/ en /news/cellular-atlas-built-guide-precision-treatment-rheumatoid-arthritis <span class="field field--name-title field--type-string field--label-hidden"><h1>Cellular atlas built to guide precision treatment of rheumatoid arthritis</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Tom Ulrich</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2023-11-07T17:33:23-05:00" class="datetime">November 7, 2023</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Cellular atlas built to guide precision treatment of rheumatoid arthritis</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Analysis of more than 314,000 cells from rheumatoid arthritis tissue defines six types of inflammation involving diverse cell types and disease pathways</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Brigham and Women's Hospital Communications </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2023-11-07T17:33:23-05:00" title="Tuesday, November 7, 2023 - 17:33" class="datetime">November 7, 2023</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=FCdaheg0 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=FCdaheg0 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=PwfX1q8e 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="736" height="520"> <source srcset="/files/styles/multiple_ct_header_laptop/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=mw0l5ceY 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="641" height="451"> <source srcset="/files/styles/multiple_ct_header_tablet/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=S5gv7ZlL 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="706" height="417"> <source srcset="/files/styles/multiple_ct_header_phone/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=fkyICH-6 1x" media="all and (max-width: 539px)" type="image/jpeg" width="499" height="294"> <img loading="eager" src="/files/styles/multiple_ct_header_phone/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=fkyICH-6" width="499" height="294" alt="Cartoon illustration of a knee with red concentric circles denoting pain from arthritis" title="Cartoon illustration of a knee with red concentric circles denoting pain from arthritis" typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__description"> </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" 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</a> <a href="mailto:?subject=&amp;body=/taxonomy/term/616/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons__button share-email" target="_blank" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-with-sidebar text-with-sidebar"> <div class="field field--name-field-sidebar field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-menu sidebar-menu"> <div class="sidebar-menu__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related people</p> </div> <div class="field field--name-field-links field--type-link field--label-hidden field__items"> <div class="field__item"><a href="/bios/soumya-raychaudhuri">Soumya Raychaudhuri</a></div> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-menu sidebar-menu"> <div class="sidebar-menu__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related programs</p> </div> <div class="field field--name-field-links field--type-link field--label-hidden field__items"> <div class="field__item"><a href="/medical-population-genetics">Program in Medical and Population Genetics</a></div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation that leads to pain, joint damage, and disability, which affects approximately 18 million people worldwide. While RA therapies targeted to specific inflammatory pathways have emerged, only some patients’ symptoms improve with treatment, emphasizing the need for multiple treatment approaches tailored to different disease subtypes. To more precisely define cellular drivers of RA, an international research consortium co-led by researchers from the ӳ����ý of MIT and Harvard and Brigham and Women’s Hospital analyzed tissues from RA donors at the single-cell level, integrating multiple forms of analysis to stratify RA by six subtypes of inflammation. The findings, published in <a href="https://www.nature.com/articles/s41586-023-06708-y" target="_blank"><em>Nature</em></a>, shed new light on the variety of cellular causes of RA, which may inform more targeted, effective and patient-tailored therapeutic approaches.</p> <p>“In the treatment of individuals with rheumatoid arthritis, we struggle to find the right treatment for the right patient,” said corresponding author <a href="/node/446111/">Soumya Raychaudhuri</a> of the Brigham’s Division of Rheumatology, Inflammation and Immunity and the ӳ����ý, where he is an institute member in the <a href="/node/8507">Program in Medical and Population Genetics</a>. “We aimed to determine why some subsets of patients don’t respond to conventional treatments by looking at the subtypes of inflammation. We did so from many different angles, using multiple cutting-edge, single-cell techniques and integrating results in a way that hasn’t been done before for an inflammatory disease.”</p> <p>The findings from the study represent a major milestone in the Accelerating Medicines Partnership Rheumatoid Arthritis and Systemic Lupus Erythematosus program, a public-private partnership launched in 2014 to advance molecular- and cellular-level understandings of autoimmune diseases and identify promising drug targets. Through collaboration with researchers and clinicians across the US and UK, the investigators analyzed 79 donor samples of synovial tissue, the inflamed tissue in RA that normally helps cushion and sustain joints. In particular, the researchers examined tissue from patients with new-onset disease and from patients unresponsive to treatment to better identify both the initial drivers of RA as well as those of refractory disease.&nbsp;</p> <p>To “deconstruct” RA pathology on a cellular level, the researchers combined surface protein data and histologic analysis with multiple forms of single-cell RNA-sequencing and bulk RNA sequencing. Despite the variety of methods used to analyze over 314,000 cells, the researchers consistently found evidence of six major types of inflammation, which they stratified by associated cell type, called cell-type abundance phenotypes (CTAPs). While some CTAPS, such as those enriched with T and B cells, were expected finding for an autoimmune disease like RA, the researchers were surprised to see CTAPs associated with structural cells such as fibroblasts and endothelial cells, with relatively few inflammatory leukocytes. They also found that patients’ CTAPs were dynamic and could change over time in response to treatment.&nbsp;</p> <p>Going forward, the researchers aim to expand upon their knowledge of the cell types involved in RA by studying how interconnections between cells promote disease states. Furthermore, they hope this work will encourage increased synovial tissue analysis in RA patients, which is currently not standard practice. While blood tests are more common in RA patients, findings from this study and others emphasize that the cellular profile of synovial tissue differs substantially from that of blood.&nbsp;</p> <p>“What this study shows is that the tissue matters,” said co-senior author Michael Brenner of the Brigham’s Division of Rheumatology, Inflammation and Immunity. “Our findings point to the value of getting synovial tissue biopsies to evaluate the nature of the pathological process, which can be so different across patients. Clinical trials going forward will benefit greatly from assessing tissue characteristics alongside responses to a therapy. By providing this atlas of cell types and pathways involved in RA, we are better able to pursue our precision medicine goal of being able to select the right drug for the right patient and achieve a high response rate.”</p> <p>Co-first authors of the study are Fan Zhang (University of Colorado Anschutz Medical Campus), Anna Helena Jonsson (BWH), Aparna Nathan (Harvard University), and Nghia Millard (BWH). Co-senior authors alongside Raychaudhuri and Brenner are Kevin Wei (BWH), Deepak Rao (BWH), Laura Donlin (Hospital for Special Surgery) and Jennifer Anolik (University of Rochester Medical Center).&nbsp;</p> <p><em>Adapted from <a href="https://www.brighamandwomens.org/about-bwh/newsroom/press-releases-detail?id=4579" target="_blank">a press release issued by Brigham and Women's Hospital</a>.</em></p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported by the Accelerating Medicines Partnership (AMP) in Rheumatoid Arthritis and Lupus Network, a public- private partnership (AbbVie, Arthritis Foundation, Bristol-Myers Squibb Company, Foundation for the National Institutes of Health, GlaxoSmithKline, Janssen Research and Development, Lupus Foundation of America, Lupus Research Alliance, Merck Sharp and Dohme, National Institute of Allergy and Infectious Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Pfizer, Rheumatology Research Foundation, Sanofi and Takeda Pharmaceuticals International). Funding was provided by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the National Human Genome Research Institute.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Zhang F, et al. “Deconstruction of rheumatoid arthritis synovium defines inflammatory subtypes.” <a href="https://www.nature.com/articles/s41586-023-06708-y" target="_blank"><em>Nature</em></a>. Online November 8, 2023.&nbsp;DOI: 10.1038/s41586-023-06708-y.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/medical-and-population-genetics" hreflang="en">Medical and Population Genetics Program</a></div> <div class="field__item"><a href="/broad-tags/immunological-disease" hreflang="en">Immunological Disease</a></div> <div class="field__item"><a href="/broad-tags/transcriptomics" hreflang="en">Transcriptomics</a></div> <div class="field__item"><a href="/broad-tags/single-cell" hreflang="en">Single Cell</a></div> <div class="field__item"><a href="/broad-tags/soumya-raychaudhuri" hreflang="en">Soumya Raychaudhuri</a></div> </div> </div> </div> </div> </div> Tue, 07 Nov 2023 22:33:23 +0000 tulrich@broadinstitute.org 5555981 at /news/researchers-develop-strategy-precisely-target-subtypes-key-protein <span class="field field--name-title field--type-string field--label-hidden"><h1>Cellular atlas built to guide precision treatment of rheumatoid arthritis</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Tom Ulrich</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2023-11-07T17:33:23-05:00" class="datetime">November 7, 2023</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Cellular atlas built to guide precision treatment of rheumatoid arthritis</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Analysis of more than 314,000 cells from rheumatoid arthritis tissue defines six types of inflammation involving diverse cell types and disease pathways</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Brigham and Women's Hospital Communications </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2023-11-07T17:33:23-05:00" title="Tuesday, November 7, 2023 - 17:33" class="datetime">November 7, 2023</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=FCdaheg0 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=FCdaheg0 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=PwfX1q8e 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="736" height="520"> <source srcset="/files/styles/multiple_ct_header_laptop/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=mw0l5ceY 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="641" height="451"> <source srcset="/files/styles/multiple_ct_header_tablet/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=S5gv7ZlL 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="706" height="417"> <source srcset="/files/styles/multiple_ct_header_phone/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=fkyICH-6 1x" media="all and (max-width: 539px)" type="image/jpeg" width="499" height="294"> <img loading="eager" src="/files/styles/multiple_ct_header_phone/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=fkyICH-6" width="499" height="294" alt="Cartoon illustration of a knee with red concentric circles denoting pain from arthritis" title="Cartoon illustration of a knee with red concentric circles denoting pain from arthritis" typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__description"> </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous"></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/616/feed&amp;title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons__button share-facebook" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/616/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons__button share-x" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&amp;body=/taxonomy/term/616/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons__button share-email" target="_blank" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-with-sidebar text-with-sidebar"> <div class="field field--name-field-sidebar field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-menu sidebar-menu"> <div class="sidebar-menu__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related people</p> </div> <div class="field field--name-field-links field--type-link field--label-hidden field__items"> <div class="field__item"><a href="/bios/soumya-raychaudhuri">Soumya Raychaudhuri</a></div> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-menu sidebar-menu"> <div class="sidebar-menu__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related programs</p> </div> <div class="field field--name-field-links field--type-link field--label-hidden field__items"> <div class="field__item"><a href="/medical-population-genetics">Program in Medical and Population Genetics</a></div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation that leads to pain, joint damage, and disability, which affects approximately 18 million people worldwide. While RA therapies targeted to specific inflammatory pathways have emerged, only some patients’ symptoms improve with treatment, emphasizing the need for multiple treatment approaches tailored to different disease subtypes. To more precisely define cellular drivers of RA, an international research consortium co-led by researchers from the ӳ����ý of MIT and Harvard and Brigham and Women’s Hospital analyzed tissues from RA donors at the single-cell level, integrating multiple forms of analysis to stratify RA by six subtypes of inflammation. The findings, published in <a href="https://www.nature.com/articles/s41586-023-06708-y" target="_blank"><em>Nature</em></a>, shed new light on the variety of cellular causes of RA, which may inform more targeted, effective and patient-tailored therapeutic approaches.</p> <p>“In the treatment of individuals with rheumatoid arthritis, we struggle to find the right treatment for the right patient,” said corresponding author <a href="/node/446111/">Soumya Raychaudhuri</a> of the Brigham’s Division of Rheumatology, Inflammation and Immunity and the ӳ����ý, where he is an institute member in the <a href="/node/8507">Program in Medical and Population Genetics</a>. “We aimed to determine why some subsets of patients don’t respond to conventional treatments by looking at the subtypes of inflammation. We did so from many different angles, using multiple cutting-edge, single-cell techniques and integrating results in a way that hasn’t been done before for an inflammatory disease.”</p> <p>The findings from the study represent a major milestone in the Accelerating Medicines Partnership Rheumatoid Arthritis and Systemic Lupus Erythematosus program, a public-private partnership launched in 2014 to advance molecular- and cellular-level understandings of autoimmune diseases and identify promising drug targets. Through collaboration with researchers and clinicians across the US and UK, the investigators analyzed 79 donor samples of synovial tissue, the inflamed tissue in RA that normally helps cushion and sustain joints. In particular, the researchers examined tissue from patients with new-onset disease and from patients unresponsive to treatment to better identify both the initial drivers of RA as well as those of refractory disease.&nbsp;</p> <p>To “deconstruct” RA pathology on a cellular level, the researchers combined surface protein data and histologic analysis with multiple forms of single-cell RNA-sequencing and bulk RNA sequencing. Despite the variety of methods used to analyze over 314,000 cells, the researchers consistently found evidence of six major types of inflammation, which they stratified by associated cell type, called cell-type abundance phenotypes (CTAPs). While some CTAPS, such as those enriched with T and B cells, were expected finding for an autoimmune disease like RA, the researchers were surprised to see CTAPs associated with structural cells such as fibroblasts and endothelial cells, with relatively few inflammatory leukocytes. They also found that patients’ CTAPs were dynamic and could change over time in response to treatment.&nbsp;</p> <p>Going forward, the researchers aim to expand upon their knowledge of the cell types involved in RA by studying how interconnections between cells promote disease states. Furthermore, they hope this work will encourage increased synovial tissue analysis in RA patients, which is currently not standard practice. While blood tests are more common in RA patients, findings from this study and others emphasize that the cellular profile of synovial tissue differs substantially from that of blood.&nbsp;</p> <p>“What this study shows is that the tissue matters,” said co-senior author Michael Brenner of the Brigham’s Division of Rheumatology, Inflammation and Immunity. “Our findings point to the value of getting synovial tissue biopsies to evaluate the nature of the pathological process, which can be so different across patients. Clinical trials going forward will benefit greatly from assessing tissue characteristics alongside responses to a therapy. By providing this atlas of cell types and pathways involved in RA, we are better able to pursue our precision medicine goal of being able to select the right drug for the right patient and achieve a high response rate.”</p> <p>Co-first authors of the study are Fan Zhang (University of Colorado Anschutz Medical Campus), Anna Helena Jonsson (BWH), Aparna Nathan (Harvard University), and Nghia Millard (BWH). Co-senior authors alongside Raychaudhuri and Brenner are Kevin Wei (BWH), Deepak Rao (BWH), Laura Donlin (Hospital for Special Surgery) and Jennifer Anolik (University of Rochester Medical Center).&nbsp;</p> <p><em>Adapted from <a href="https://www.brighamandwomens.org/about-bwh/newsroom/press-releases-detail?id=4579" target="_blank">a press release issued by Brigham and Women's Hospital</a>.</em></p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported by the Accelerating Medicines Partnership (AMP) in Rheumatoid Arthritis and Lupus Network, a public- private partnership (AbbVie, Arthritis Foundation, Bristol-Myers Squibb Company, Foundation for the National Institutes of Health, GlaxoSmithKline, Janssen Research and Development, Lupus Foundation of America, Lupus Research Alliance, Merck Sharp and Dohme, National Institute of Allergy and Infectious Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Pfizer, Rheumatology Research Foundation, Sanofi and Takeda Pharmaceuticals International). Funding was provided by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the National Human Genome Research Institute.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Zhang F, et al. “Deconstruction of rheumatoid arthritis synovium defines inflammatory subtypes.” <a href="https://www.nature.com/articles/s41586-023-06708-y" target="_blank"><em>Nature</em></a>. Online November 8, 2023.&nbsp;DOI: 10.1038/s41586-023-06708-y.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/medical-and-population-genetics" hreflang="en">Medical and Population Genetics Program</a></div> <div class="field__item"><a href="/broad-tags/immunological-disease" hreflang="en">Immunological Disease</a></div> <div class="field__item"><a href="/broad-tags/transcriptomics" hreflang="en">Transcriptomics</a></div> <div class="field__item"><a href="/broad-tags/single-cell" hreflang="en">Single Cell</a></div> <div class="field__item"><a href="/broad-tags/soumya-raychaudhuri" hreflang="en">Soumya Raychaudhuri</a></div> </div> </div> </div> </div> </div> Mon, 26 Sep 2022 19:10:06 +0000 aviveros@broadinstitute.org 1202331 at /news/exploring-autoimmunitys-regulatory-roots <span class="field field--name-title field--type-string field--label-hidden"><h1>Cellular atlas built to guide precision treatment of rheumatoid arthritis</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Tom Ulrich</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2023-11-07T17:33:23-05:00" class="datetime">November 7, 2023</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Cellular atlas built to guide precision treatment of rheumatoid arthritis</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Analysis of more than 314,000 cells from rheumatoid arthritis tissue defines six types of inflammation involving diverse cell types and disease pathways</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Brigham and Women's Hospital Communications </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2023-11-07T17:33:23-05:00" title="Tuesday, November 7, 2023 - 17:33" class="datetime">November 7, 2023</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=FCdaheg0 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=FCdaheg0 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=PwfX1q8e 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="736" height="520"> <source srcset="/files/styles/multiple_ct_header_laptop/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=mw0l5ceY 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="641" height="451"> <source srcset="/files/styles/multiple_ct_header_tablet/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=S5gv7ZlL 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="706" height="417"> <source srcset="/files/styles/multiple_ct_header_phone/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=fkyICH-6 1x" media="all and (max-width: 539px)" type="image/jpeg" width="499" height="294"> <img loading="eager" src="/files/styles/multiple_ct_header_phone/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=fkyICH-6" width="499" height="294" alt="Cartoon illustration of a knee with red concentric circles denoting pain from arthritis" title="Cartoon illustration of a knee with red concentric circles denoting pain from arthritis" typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__description"> </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous"></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/616/feed&amp;title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons__button share-facebook" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/616/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons__button share-x" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&amp;body=/taxonomy/term/616/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons__button share-email" target="_blank" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-with-sidebar text-with-sidebar"> <div class="field field--name-field-sidebar field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-menu sidebar-menu"> <div class="sidebar-menu__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related people</p> </div> <div class="field field--name-field-links field--type-link field--label-hidden field__items"> <div class="field__item"><a href="/bios/soumya-raychaudhuri">Soumya Raychaudhuri</a></div> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-menu sidebar-menu"> <div class="sidebar-menu__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related programs</p> </div> <div class="field field--name-field-links field--type-link field--label-hidden field__items"> <div class="field__item"><a href="/medical-population-genetics">Program in Medical and Population Genetics</a></div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation that leads to pain, joint damage, and disability, which affects approximately 18 million people worldwide. While RA therapies targeted to specific inflammatory pathways have emerged, only some patients’ symptoms improve with treatment, emphasizing the need for multiple treatment approaches tailored to different disease subtypes. To more precisely define cellular drivers of RA, an international research consortium co-led by researchers from the ӳ����ý of MIT and Harvard and Brigham and Women’s Hospital analyzed tissues from RA donors at the single-cell level, integrating multiple forms of analysis to stratify RA by six subtypes of inflammation. The findings, published in <a href="https://www.nature.com/articles/s41586-023-06708-y" target="_blank"><em>Nature</em></a>, shed new light on the variety of cellular causes of RA, which may inform more targeted, effective and patient-tailored therapeutic approaches.</p> <p>“In the treatment of individuals with rheumatoid arthritis, we struggle to find the right treatment for the right patient,” said corresponding author <a href="/node/446111/">Soumya Raychaudhuri</a> of the Brigham’s Division of Rheumatology, Inflammation and Immunity and the ӳ����ý, where he is an institute member in the <a href="/node/8507">Program in Medical and Population Genetics</a>. “We aimed to determine why some subsets of patients don’t respond to conventional treatments by looking at the subtypes of inflammation. We did so from many different angles, using multiple cutting-edge, single-cell techniques and integrating results in a way that hasn’t been done before for an inflammatory disease.”</p> <p>The findings from the study represent a major milestone in the Accelerating Medicines Partnership Rheumatoid Arthritis and Systemic Lupus Erythematosus program, a public-private partnership launched in 2014 to advance molecular- and cellular-level understandings of autoimmune diseases and identify promising drug targets. Through collaboration with researchers and clinicians across the US and UK, the investigators analyzed 79 donor samples of synovial tissue, the inflamed tissue in RA that normally helps cushion and sustain joints. In particular, the researchers examined tissue from patients with new-onset disease and from patients unresponsive to treatment to better identify both the initial drivers of RA as well as those of refractory disease.&nbsp;</p> <p>To “deconstruct” RA pathology on a cellular level, the researchers combined surface protein data and histologic analysis with multiple forms of single-cell RNA-sequencing and bulk RNA sequencing. Despite the variety of methods used to analyze over 314,000 cells, the researchers consistently found evidence of six major types of inflammation, which they stratified by associated cell type, called cell-type abundance phenotypes (CTAPs). While some CTAPS, such as those enriched with T and B cells, were expected finding for an autoimmune disease like RA, the researchers were surprised to see CTAPs associated with structural cells such as fibroblasts and endothelial cells, with relatively few inflammatory leukocytes. They also found that patients’ CTAPs were dynamic and could change over time in response to treatment.&nbsp;</p> <p>Going forward, the researchers aim to expand upon their knowledge of the cell types involved in RA by studying how interconnections between cells promote disease states. Furthermore, they hope this work will encourage increased synovial tissue analysis in RA patients, which is currently not standard practice. While blood tests are more common in RA patients, findings from this study and others emphasize that the cellular profile of synovial tissue differs substantially from that of blood.&nbsp;</p> <p>“What this study shows is that the tissue matters,” said co-senior author Michael Brenner of the Brigham’s Division of Rheumatology, Inflammation and Immunity. “Our findings point to the value of getting synovial tissue biopsies to evaluate the nature of the pathological process, which can be so different across patients. Clinical trials going forward will benefit greatly from assessing tissue characteristics alongside responses to a therapy. By providing this atlas of cell types and pathways involved in RA, we are better able to pursue our precision medicine goal of being able to select the right drug for the right patient and achieve a high response rate.”</p> <p>Co-first authors of the study are Fan Zhang (University of Colorado Anschutz Medical Campus), Anna Helena Jonsson (BWH), Aparna Nathan (Harvard University), and Nghia Millard (BWH). Co-senior authors alongside Raychaudhuri and Brenner are Kevin Wei (BWH), Deepak Rao (BWH), Laura Donlin (Hospital for Special Surgery) and Jennifer Anolik (University of Rochester Medical Center).&nbsp;</p> <p><em>Adapted from <a href="https://www.brighamandwomens.org/about-bwh/newsroom/press-releases-detail?id=4579" target="_blank">a press release issued by Brigham and Women's Hospital</a>.</em></p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported by the Accelerating Medicines Partnership (AMP) in Rheumatoid Arthritis and Lupus Network, a public- private partnership (AbbVie, Arthritis Foundation, Bristol-Myers Squibb Company, Foundation for the National Institutes of Health, GlaxoSmithKline, Janssen Research and Development, Lupus Foundation of America, Lupus Research Alliance, Merck Sharp and Dohme, National Institute of Allergy and Infectious Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Pfizer, Rheumatology Research Foundation, Sanofi and Takeda Pharmaceuticals International). Funding was provided by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the National Human Genome Research Institute.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Zhang F, et al. “Deconstruction of rheumatoid arthritis synovium defines inflammatory subtypes.” <a href="https://www.nature.com/articles/s41586-023-06708-y" target="_blank"><em>Nature</em></a>. Online November 8, 2023.&nbsp;DOI: 10.1038/s41586-023-06708-y.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/medical-and-population-genetics" hreflang="en">Medical and Population Genetics Program</a></div> <div class="field__item"><a href="/broad-tags/immunological-disease" hreflang="en">Immunological Disease</a></div> <div class="field__item"><a href="/broad-tags/transcriptomics" hreflang="en">Transcriptomics</a></div> <div class="field__item"><a href="/broad-tags/single-cell" hreflang="en">Single Cell</a></div> <div class="field__item"><a href="/broad-tags/soumya-raychaudhuri" hreflang="en">Soumya Raychaudhuri</a></div> </div> </div> </div> </div> </div> Fri, 06 May 2022 13:30:21 +0000 tulrich@broadinstitute.org 1131936 at /news/researchers-pinpoint-genes-behind-sex-biases-autoimmune-disorders-schizophrenia <span class="field field--name-title field--type-string field--label-hidden"><h1>Cellular atlas built to guide precision treatment of rheumatoid arthritis</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Tom Ulrich</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2023-11-07T17:33:23-05:00" class="datetime">November 7, 2023</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Cellular atlas built to guide precision treatment of rheumatoid arthritis</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Analysis of more than 314,000 cells from rheumatoid arthritis tissue defines six types of inflammation involving diverse cell types and disease pathways</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Brigham and Women's Hospital Communications </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2023-11-07T17:33:23-05:00" title="Tuesday, November 7, 2023 - 17:33" class="datetime">November 7, 2023</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=FCdaheg0 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=FCdaheg0 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=PwfX1q8e 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="736" height="520"> <source srcset="/files/styles/multiple_ct_header_laptop/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=mw0l5ceY 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="641" height="451"> <source srcset="/files/styles/multiple_ct_header_tablet/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=S5gv7ZlL 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="706" height="417"> <source srcset="/files/styles/multiple_ct_header_phone/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=fkyICH-6 1x" media="all and (max-width: 539px)" type="image/jpeg" width="499" height="294"> <img loading="eager" src="/files/styles/multiple_ct_header_phone/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=fkyICH-6" width="499" height="294" alt="Cartoon illustration of a knee with red concentric circles denoting pain from arthritis" title="Cartoon illustration of a knee with red concentric circles denoting pain from arthritis" typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__description"> </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div 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width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&amp;body=/taxonomy/term/616/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons__button share-email" target="_blank" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-with-sidebar text-with-sidebar"> <div class="field field--name-field-sidebar field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-menu sidebar-menu"> <div class="sidebar-menu__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related people</p> </div> <div class="field field--name-field-links field--type-link field--label-hidden field__items"> <div class="field__item"><a href="/bios/soumya-raychaudhuri">Soumya Raychaudhuri</a></div> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-menu sidebar-menu"> <div class="sidebar-menu__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related programs</p> </div> <div class="field field--name-field-links field--type-link field--label-hidden field__items"> <div class="field__item"><a href="/medical-population-genetics">Program in Medical and Population Genetics</a></div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation that leads to pain, joint damage, and disability, which affects approximately 18 million people worldwide. While RA therapies targeted to specific inflammatory pathways have emerged, only some patients’ symptoms improve with treatment, emphasizing the need for multiple treatment approaches tailored to different disease subtypes. To more precisely define cellular drivers of RA, an international research consortium co-led by researchers from the ӳ����ý of MIT and Harvard and Brigham and Women’s Hospital analyzed tissues from RA donors at the single-cell level, integrating multiple forms of analysis to stratify RA by six subtypes of inflammation. The findings, published in <a href="https://www.nature.com/articles/s41586-023-06708-y" target="_blank"><em>Nature</em></a>, shed new light on the variety of cellular causes of RA, which may inform more targeted, effective and patient-tailored therapeutic approaches.</p> <p>“In the treatment of individuals with rheumatoid arthritis, we struggle to find the right treatment for the right patient,” said corresponding author <a href="/node/446111/">Soumya Raychaudhuri</a> of the Brigham’s Division of Rheumatology, Inflammation and Immunity and the ӳ����ý, where he is an institute member in the <a href="/node/8507">Program in Medical and Population Genetics</a>. “We aimed to determine why some subsets of patients don’t respond to conventional treatments by looking at the subtypes of inflammation. We did so from many different angles, using multiple cutting-edge, single-cell techniques and integrating results in a way that hasn’t been done before for an inflammatory disease.”</p> <p>The findings from the study represent a major milestone in the Accelerating Medicines Partnership Rheumatoid Arthritis and Systemic Lupus Erythematosus program, a public-private partnership launched in 2014 to advance molecular- and cellular-level understandings of autoimmune diseases and identify promising drug targets. Through collaboration with researchers and clinicians across the US and UK, the investigators analyzed 79 donor samples of synovial tissue, the inflamed tissue in RA that normally helps cushion and sustain joints. In particular, the researchers examined tissue from patients with new-onset disease and from patients unresponsive to treatment to better identify both the initial drivers of RA as well as those of refractory disease.&nbsp;</p> <p>To “deconstruct” RA pathology on a cellular level, the researchers combined surface protein data and histologic analysis with multiple forms of single-cell RNA-sequencing and bulk RNA sequencing. Despite the variety of methods used to analyze over 314,000 cells, the researchers consistently found evidence of six major types of inflammation, which they stratified by associated cell type, called cell-type abundance phenotypes (CTAPs). While some CTAPS, such as those enriched with T and B cells, were expected finding for an autoimmune disease like RA, the researchers were surprised to see CTAPs associated with structural cells such as fibroblasts and endothelial cells, with relatively few inflammatory leukocytes. They also found that patients’ CTAPs were dynamic and could change over time in response to treatment.&nbsp;</p> <p>Going forward, the researchers aim to expand upon their knowledge of the cell types involved in RA by studying how interconnections between cells promote disease states. Furthermore, they hope this work will encourage increased synovial tissue analysis in RA patients, which is currently not standard practice. While blood tests are more common in RA patients, findings from this study and others emphasize that the cellular profile of synovial tissue differs substantially from that of blood.&nbsp;</p> <p>“What this study shows is that the tissue matters,” said co-senior author Michael Brenner of the Brigham’s Division of Rheumatology, Inflammation and Immunity. “Our findings point to the value of getting synovial tissue biopsies to evaluate the nature of the pathological process, which can be so different across patients. Clinical trials going forward will benefit greatly from assessing tissue characteristics alongside responses to a therapy. By providing this atlas of cell types and pathways involved in RA, we are better able to pursue our precision medicine goal of being able to select the right drug for the right patient and achieve a high response rate.”</p> <p>Co-first authors of the study are Fan Zhang (University of Colorado Anschutz Medical Campus), Anna Helena Jonsson (BWH), Aparna Nathan (Harvard University), and Nghia Millard (BWH). Co-senior authors alongside Raychaudhuri and Brenner are Kevin Wei (BWH), Deepak Rao (BWH), Laura Donlin (Hospital for Special Surgery) and Jennifer Anolik (University of Rochester Medical Center).&nbsp;</p> <p><em>Adapted from <a href="https://www.brighamandwomens.org/about-bwh/newsroom/press-releases-detail?id=4579" target="_blank">a press release issued by Brigham and Women's Hospital</a>.</em></p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported by the Accelerating Medicines Partnership (AMP) in Rheumatoid Arthritis and Lupus Network, a public- private partnership (AbbVie, Arthritis Foundation, Bristol-Myers Squibb Company, Foundation for the National Institutes of Health, GlaxoSmithKline, Janssen Research and Development, Lupus Foundation of America, Lupus Research Alliance, Merck Sharp and Dohme, National Institute of Allergy and Infectious Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Pfizer, Rheumatology Research Foundation, Sanofi and Takeda Pharmaceuticals International). Funding was provided by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the National Human Genome Research Institute.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Zhang F, et al. “Deconstruction of rheumatoid arthritis synovium defines inflammatory subtypes.” <a href="https://www.nature.com/articles/s41586-023-06708-y" target="_blank"><em>Nature</em></a>. Online November 8, 2023.&nbsp;DOI: 10.1038/s41586-023-06708-y.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/medical-and-population-genetics" hreflang="en">Medical and Population Genetics Program</a></div> <div class="field__item"><a href="/broad-tags/immunological-disease" hreflang="en">Immunological Disease</a></div> <div class="field__item"><a href="/broad-tags/transcriptomics" hreflang="en">Transcriptomics</a></div> <div class="field__item"><a href="/broad-tags/single-cell" hreflang="en">Single Cell</a></div> <div class="field__item"><a href="/broad-tags/soumya-raychaudhuri" hreflang="en">Soumya Raychaudhuri</a></div> </div> </div> </div> </div> </div> Mon, 11 May 2020 15:01:21 +0000 tulrich@broadinstitute.org 628561 at /news/how-immune-system-puts-brakes-allergic-inflammation <span class="field field--name-title field--type-string field--label-hidden"><h1>Cellular atlas built to guide precision treatment of rheumatoid arthritis</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Tom Ulrich</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2023-11-07T17:33:23-05:00" class="datetime">November 7, 2023</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Cellular atlas built to guide precision treatment of rheumatoid arthritis</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Analysis of more than 314,000 cells from rheumatoid arthritis tissue defines six types of inflammation involving diverse cell types and disease pathways</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Brigham and Women's Hospital Communications </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2023-11-07T17:33:23-05:00" title="Tuesday, November 7, 2023 - 17:33" class="datetime">November 7, 2023</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=FCdaheg0 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=FCdaheg0 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=PwfX1q8e 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="736" height="520"> <source srcset="/files/styles/multiple_ct_header_laptop/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=mw0l5ceY 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="641" height="451"> <source srcset="/files/styles/multiple_ct_header_tablet/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=S5gv7ZlL 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="706" height="417"> <source srcset="/files/styles/multiple_ct_header_phone/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=fkyICH-6 1x" media="all and (max-width: 539px)" type="image/jpeg" width="499" height="294"> <img loading="eager" src="/files/styles/multiple_ct_header_phone/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=fkyICH-6" width="499" height="294" alt="Cartoon illustration of a knee with red concentric circles denoting pain from arthritis" title="Cartoon illustration of a knee with red concentric circles denoting pain from arthritis" typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__description"> </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous"></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/616/feed&amp;title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons__button share-facebook" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/616/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons__button share-x" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&amp;body=/taxonomy/term/616/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons__button share-email" target="_blank" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-with-sidebar text-with-sidebar"> <div class="field field--name-field-sidebar field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-menu sidebar-menu"> <div class="sidebar-menu__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related people</p> </div> <div class="field field--name-field-links field--type-link field--label-hidden field__items"> <div class="field__item"><a href="/bios/soumya-raychaudhuri">Soumya Raychaudhuri</a></div> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-menu sidebar-menu"> <div class="sidebar-menu__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related programs</p> </div> <div class="field field--name-field-links field--type-link field--label-hidden field__items"> <div class="field__item"><a href="/medical-population-genetics">Program in Medical and Population Genetics</a></div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation that leads to pain, joint damage, and disability, which affects approximately 18 million people worldwide. While RA therapies targeted to specific inflammatory pathways have emerged, only some patients’ symptoms improve with treatment, emphasizing the need for multiple treatment approaches tailored to different disease subtypes. To more precisely define cellular drivers of RA, an international research consortium co-led by researchers from the ӳ����ý of MIT and Harvard and Brigham and Women’s Hospital analyzed tissues from RA donors at the single-cell level, integrating multiple forms of analysis to stratify RA by six subtypes of inflammation. The findings, published in <a href="https://www.nature.com/articles/s41586-023-06708-y" target="_blank"><em>Nature</em></a>, shed new light on the variety of cellular causes of RA, which may inform more targeted, effective and patient-tailored therapeutic approaches.</p> <p>“In the treatment of individuals with rheumatoid arthritis, we struggle to find the right treatment for the right patient,” said corresponding author <a href="/node/446111/">Soumya Raychaudhuri</a> of the Brigham’s Division of Rheumatology, Inflammation and Immunity and the ӳ����ý, where he is an institute member in the <a href="/node/8507">Program in Medical and Population Genetics</a>. “We aimed to determine why some subsets of patients don’t respond to conventional treatments by looking at the subtypes of inflammation. We did so from many different angles, using multiple cutting-edge, single-cell techniques and integrating results in a way that hasn’t been done before for an inflammatory disease.”</p> <p>The findings from the study represent a major milestone in the Accelerating Medicines Partnership Rheumatoid Arthritis and Systemic Lupus Erythematosus program, a public-private partnership launched in 2014 to advance molecular- and cellular-level understandings of autoimmune diseases and identify promising drug targets. Through collaboration with researchers and clinicians across the US and UK, the investigators analyzed 79 donor samples of synovial tissue, the inflamed tissue in RA that normally helps cushion and sustain joints. In particular, the researchers examined tissue from patients with new-onset disease and from patients unresponsive to treatment to better identify both the initial drivers of RA as well as those of refractory disease.&nbsp;</p> <p>To “deconstruct” RA pathology on a cellular level, the researchers combined surface protein data and histologic analysis with multiple forms of single-cell RNA-sequencing and bulk RNA sequencing. Despite the variety of methods used to analyze over 314,000 cells, the researchers consistently found evidence of six major types of inflammation, which they stratified by associated cell type, called cell-type abundance phenotypes (CTAPs). While some CTAPS, such as those enriched with T and B cells, were expected finding for an autoimmune disease like RA, the researchers were surprised to see CTAPs associated with structural cells such as fibroblasts and endothelial cells, with relatively few inflammatory leukocytes. They also found that patients’ CTAPs were dynamic and could change over time in response to treatment.&nbsp;</p> <p>Going forward, the researchers aim to expand upon their knowledge of the cell types involved in RA by studying how interconnections between cells promote disease states. Furthermore, they hope this work will encourage increased synovial tissue analysis in RA patients, which is currently not standard practice. While blood tests are more common in RA patients, findings from this study and others emphasize that the cellular profile of synovial tissue differs substantially from that of blood.&nbsp;</p> <p>“What this study shows is that the tissue matters,” said co-senior author Michael Brenner of the Brigham’s Division of Rheumatology, Inflammation and Immunity. “Our findings point to the value of getting synovial tissue biopsies to evaluate the nature of the pathological process, which can be so different across patients. Clinical trials going forward will benefit greatly from assessing tissue characteristics alongside responses to a therapy. By providing this atlas of cell types and pathways involved in RA, we are better able to pursue our precision medicine goal of being able to select the right drug for the right patient and achieve a high response rate.”</p> <p>Co-first authors of the study are Fan Zhang (University of Colorado Anschutz Medical Campus), Anna Helena Jonsson (BWH), Aparna Nathan (Harvard University), and Nghia Millard (BWH). Co-senior authors alongside Raychaudhuri and Brenner are Kevin Wei (BWH), Deepak Rao (BWH), Laura Donlin (Hospital for Special Surgery) and Jennifer Anolik (University of Rochester Medical Center).&nbsp;</p> <p><em>Adapted from <a href="https://www.brighamandwomens.org/about-bwh/newsroom/press-releases-detail?id=4579" target="_blank">a press release issued by Brigham and Women's Hospital</a>.</em></p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported by the Accelerating Medicines Partnership (AMP) in Rheumatoid Arthritis and Lupus Network, a public- private partnership (AbbVie, Arthritis Foundation, Bristol-Myers Squibb Company, Foundation for the National Institutes of Health, GlaxoSmithKline, Janssen Research and Development, Lupus Foundation of America, Lupus Research Alliance, Merck Sharp and Dohme, National Institute of Allergy and Infectious Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Pfizer, Rheumatology Research Foundation, Sanofi and Takeda Pharmaceuticals International). Funding was provided by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the National Human Genome Research Institute.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Zhang F, et al. “Deconstruction of rheumatoid arthritis synovium defines inflammatory subtypes.” <a href="https://www.nature.com/articles/s41586-023-06708-y" target="_blank"><em>Nature</em></a>. Online November 8, 2023.&nbsp;DOI: 10.1038/s41586-023-06708-y.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/medical-and-population-genetics" hreflang="en">Medical and Population Genetics Program</a></div> <div class="field__item"><a href="/broad-tags/immunological-disease" hreflang="en">Immunological Disease</a></div> <div class="field__item"><a href="/broad-tags/transcriptomics" hreflang="en">Transcriptomics</a></div> <div class="field__item"><a href="/broad-tags/single-cell" hreflang="en">Single Cell</a></div> <div class="field__item"><a href="/broad-tags/soumya-raychaudhuri" hreflang="en">Soumya Raychaudhuri</a></div> </div> </div> </div> </div> </div> Fri, 22 Nov 2019 15:00:00 +0000 kzusi@broadinstitute.org 625251 at /blog/how-improve-therapies-inflammatory-bowel-disease <span class="field field--name-title field--type-string field--label-hidden"><h1>Cellular atlas built to guide precision treatment of rheumatoid arthritis</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Tom Ulrich</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2023-11-07T17:33:23-05:00" class="datetime">November 7, 2023</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Cellular atlas built to guide precision treatment of rheumatoid arthritis</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Analysis of more than 314,000 cells from rheumatoid arthritis tissue defines six types of inflammation involving diverse cell types and disease pathways</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Brigham and Women's Hospital Communications </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2023-11-07T17:33:23-05:00" title="Tuesday, November 7, 2023 - 17:33" class="datetime">November 7, 2023</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=FCdaheg0 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=FCdaheg0 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=PwfX1q8e 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="736" height="520"> <source srcset="/files/styles/multiple_ct_header_laptop/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=mw0l5ceY 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="641" height="451"> <source srcset="/files/styles/multiple_ct_header_tablet/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=S5gv7ZlL 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="706" height="417"> <source srcset="/files/styles/multiple_ct_header_phone/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=fkyICH-6 1x" media="all and (max-width: 539px)" type="image/jpeg" width="499" height="294"> <img loading="eager" src="/files/styles/multiple_ct_header_phone/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=fkyICH-6" width="499" height="294" alt="Cartoon illustration of a knee with red concentric circles denoting pain from arthritis" title="Cartoon illustration of a knee with red concentric circles denoting pain from arthritis" typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__description"> </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous"></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/616/feed&amp;title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons__button share-facebook" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/616/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons__button share-x" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&amp;body=/taxonomy/term/616/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons__button share-email" target="_blank" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-with-sidebar text-with-sidebar"> <div class="field field--name-field-sidebar field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-menu sidebar-menu"> <div class="sidebar-menu__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related people</p> </div> <div class="field field--name-field-links field--type-link field--label-hidden field__items"> <div class="field__item"><a href="/bios/soumya-raychaudhuri">Soumya Raychaudhuri</a></div> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-menu sidebar-menu"> <div class="sidebar-menu__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related programs</p> </div> <div class="field field--name-field-links field--type-link field--label-hidden field__items"> <div class="field__item"><a href="/medical-population-genetics">Program in Medical and Population Genetics</a></div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation that leads to pain, joint damage, and disability, which affects approximately 18 million people worldwide. While RA therapies targeted to specific inflammatory pathways have emerged, only some patients’ symptoms improve with treatment, emphasizing the need for multiple treatment approaches tailored to different disease subtypes. To more precisely define cellular drivers of RA, an international research consortium co-led by researchers from the ӳ����ý of MIT and Harvard and Brigham and Women’s Hospital analyzed tissues from RA donors at the single-cell level, integrating multiple forms of analysis to stratify RA by six subtypes of inflammation. The findings, published in <a href="https://www.nature.com/articles/s41586-023-06708-y" target="_blank"><em>Nature</em></a>, shed new light on the variety of cellular causes of RA, which may inform more targeted, effective and patient-tailored therapeutic approaches.</p> <p>“In the treatment of individuals with rheumatoid arthritis, we struggle to find the right treatment for the right patient,” said corresponding author <a href="/node/446111/">Soumya Raychaudhuri</a> of the Brigham’s Division of Rheumatology, Inflammation and Immunity and the ӳ����ý, where he is an institute member in the <a href="/node/8507">Program in Medical and Population Genetics</a>. “We aimed to determine why some subsets of patients don’t respond to conventional treatments by looking at the subtypes of inflammation. We did so from many different angles, using multiple cutting-edge, single-cell techniques and integrating results in a way that hasn’t been done before for an inflammatory disease.”</p> <p>The findings from the study represent a major milestone in the Accelerating Medicines Partnership Rheumatoid Arthritis and Systemic Lupus Erythematosus program, a public-private partnership launched in 2014 to advance molecular- and cellular-level understandings of autoimmune diseases and identify promising drug targets. Through collaboration with researchers and clinicians across the US and UK, the investigators analyzed 79 donor samples of synovial tissue, the inflamed tissue in RA that normally helps cushion and sustain joints. In particular, the researchers examined tissue from patients with new-onset disease and from patients unresponsive to treatment to better identify both the initial drivers of RA as well as those of refractory disease.&nbsp;</p> <p>To “deconstruct” RA pathology on a cellular level, the researchers combined surface protein data and histologic analysis with multiple forms of single-cell RNA-sequencing and bulk RNA sequencing. Despite the variety of methods used to analyze over 314,000 cells, the researchers consistently found evidence of six major types of inflammation, which they stratified by associated cell type, called cell-type abundance phenotypes (CTAPs). While some CTAPS, such as those enriched with T and B cells, were expected finding for an autoimmune disease like RA, the researchers were surprised to see CTAPs associated with structural cells such as fibroblasts and endothelial cells, with relatively few inflammatory leukocytes. They also found that patients’ CTAPs were dynamic and could change over time in response to treatment.&nbsp;</p> <p>Going forward, the researchers aim to expand upon their knowledge of the cell types involved in RA by studying how interconnections between cells promote disease states. Furthermore, they hope this work will encourage increased synovial tissue analysis in RA patients, which is currently not standard practice. While blood tests are more common in RA patients, findings from this study and others emphasize that the cellular profile of synovial tissue differs substantially from that of blood.&nbsp;</p> <p>“What this study shows is that the tissue matters,” said co-senior author Michael Brenner of the Brigham’s Division of Rheumatology, Inflammation and Immunity. “Our findings point to the value of getting synovial tissue biopsies to evaluate the nature of the pathological process, which can be so different across patients. Clinical trials going forward will benefit greatly from assessing tissue characteristics alongside responses to a therapy. By providing this atlas of cell types and pathways involved in RA, we are better able to pursue our precision medicine goal of being able to select the right drug for the right patient and achieve a high response rate.”</p> <p>Co-first authors of the study are Fan Zhang (University of Colorado Anschutz Medical Campus), Anna Helena Jonsson (BWH), Aparna Nathan (Harvard University), and Nghia Millard (BWH). Co-senior authors alongside Raychaudhuri and Brenner are Kevin Wei (BWH), Deepak Rao (BWH), Laura Donlin (Hospital for Special Surgery) and Jennifer Anolik (University of Rochester Medical Center).&nbsp;</p> <p><em>Adapted from <a href="https://www.brighamandwomens.org/about-bwh/newsroom/press-releases-detail?id=4579" target="_blank">a press release issued by Brigham and Women's Hospital</a>.</em></p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported by the Accelerating Medicines Partnership (AMP) in Rheumatoid Arthritis and Lupus Network, a public- private partnership (AbbVie, Arthritis Foundation, Bristol-Myers Squibb Company, Foundation for the National Institutes of Health, GlaxoSmithKline, Janssen Research and Development, Lupus Foundation of America, Lupus Research Alliance, Merck Sharp and Dohme, National Institute of Allergy and Infectious Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Pfizer, Rheumatology Research Foundation, Sanofi and Takeda Pharmaceuticals International). Funding was provided by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the National Human Genome Research Institute.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Zhang F, et al. “Deconstruction of rheumatoid arthritis synovium defines inflammatory subtypes.” <a href="https://www.nature.com/articles/s41586-023-06708-y" target="_blank"><em>Nature</em></a>. Online November 8, 2023.&nbsp;DOI: 10.1038/s41586-023-06708-y.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/medical-and-population-genetics" hreflang="en">Medical and Population Genetics Program</a></div> <div class="field__item"><a href="/broad-tags/immunological-disease" hreflang="en">Immunological Disease</a></div> <div class="field__item"><a href="/broad-tags/transcriptomics" hreflang="en">Transcriptomics</a></div> <div class="field__item"><a href="/broad-tags/single-cell" hreflang="en">Single Cell</a></div> <div class="field__item"><a href="/broad-tags/soumya-raychaudhuri" hreflang="en">Soumya Raychaudhuri</a></div> </div> </div> </div> </div> </div> Mon, 07 Oct 2019 18:02:56 +0000 Karen Blum 622506 at /news/single-cell-atlas-reveals-underlying-building-blocks-ulcerative-colitis <span class="field field--name-title field--type-string field--label-hidden"><h1>Cellular atlas built to guide precision treatment of rheumatoid arthritis</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Tom Ulrich</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2023-11-07T17:33:23-05:00" class="datetime">November 7, 2023</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Cellular atlas built to guide precision treatment of rheumatoid arthritis</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Analysis of more than 314,000 cells from rheumatoid arthritis tissue defines six types of inflammation involving diverse cell types and disease pathways</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Brigham and Women's Hospital Communications </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2023-11-07T17:33:23-05:00" title="Tuesday, November 7, 2023 - 17:33" class="datetime">November 7, 2023</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=FCdaheg0 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=FCdaheg0 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=PwfX1q8e 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="736" height="520"> <source srcset="/files/styles/multiple_ct_header_laptop/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=mw0l5ceY 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="641" height="451"> <source srcset="/files/styles/multiple_ct_header_tablet/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=S5gv7ZlL 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="706" height="417"> <source srcset="/files/styles/multiple_ct_header_phone/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=fkyICH-6 1x" media="all and (max-width: 539px)" type="image/jpeg" width="499" height="294"> <img loading="eager" src="/files/styles/multiple_ct_header_phone/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=fkyICH-6" width="499" height="294" alt="Cartoon illustration of a knee with red concentric circles denoting pain from arthritis" title="Cartoon illustration of a knee with red concentric circles denoting pain from arthritis" typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__description"> </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous"></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/616/feed&amp;title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons__button share-facebook" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/616/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons__button share-x" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&amp;body=/taxonomy/term/616/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons__button share-email" target="_blank" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-with-sidebar text-with-sidebar"> <div class="field field--name-field-sidebar field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-menu sidebar-menu"> <div class="sidebar-menu__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related people</p> </div> <div class="field field--name-field-links field--type-link field--label-hidden field__items"> <div class="field__item"><a href="/bios/soumya-raychaudhuri">Soumya Raychaudhuri</a></div> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-menu sidebar-menu"> <div class="sidebar-menu__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related programs</p> </div> <div class="field field--name-field-links field--type-link field--label-hidden field__items"> <div class="field__item"><a href="/medical-population-genetics">Program in Medical and Population Genetics</a></div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation that leads to pain, joint damage, and disability, which affects approximately 18 million people worldwide. While RA therapies targeted to specific inflammatory pathways have emerged, only some patients’ symptoms improve with treatment, emphasizing the need for multiple treatment approaches tailored to different disease subtypes. To more precisely define cellular drivers of RA, an international research consortium co-led by researchers from the ӳ����ý of MIT and Harvard and Brigham and Women’s Hospital analyzed tissues from RA donors at the single-cell level, integrating multiple forms of analysis to stratify RA by six subtypes of inflammation. The findings, published in <a href="https://www.nature.com/articles/s41586-023-06708-y" target="_blank"><em>Nature</em></a>, shed new light on the variety of cellular causes of RA, which may inform more targeted, effective and patient-tailored therapeutic approaches.</p> <p>“In the treatment of individuals with rheumatoid arthritis, we struggle to find the right treatment for the right patient,” said corresponding author <a href="/node/446111/">Soumya Raychaudhuri</a> of the Brigham’s Division of Rheumatology, Inflammation and Immunity and the ӳ����ý, where he is an institute member in the <a href="/node/8507">Program in Medical and Population Genetics</a>. “We aimed to determine why some subsets of patients don’t respond to conventional treatments by looking at the subtypes of inflammation. We did so from many different angles, using multiple cutting-edge, single-cell techniques and integrating results in a way that hasn’t been done before for an inflammatory disease.”</p> <p>The findings from the study represent a major milestone in the Accelerating Medicines Partnership Rheumatoid Arthritis and Systemic Lupus Erythematosus program, a public-private partnership launched in 2014 to advance molecular- and cellular-level understandings of autoimmune diseases and identify promising drug targets. Through collaboration with researchers and clinicians across the US and UK, the investigators analyzed 79 donor samples of synovial tissue, the inflamed tissue in RA that normally helps cushion and sustain joints. In particular, the researchers examined tissue from patients with new-onset disease and from patients unresponsive to treatment to better identify both the initial drivers of RA as well as those of refractory disease.&nbsp;</p> <p>To “deconstruct” RA pathology on a cellular level, the researchers combined surface protein data and histologic analysis with multiple forms of single-cell RNA-sequencing and bulk RNA sequencing. Despite the variety of methods used to analyze over 314,000 cells, the researchers consistently found evidence of six major types of inflammation, which they stratified by associated cell type, called cell-type abundance phenotypes (CTAPs). While some CTAPS, such as those enriched with T and B cells, were expected finding for an autoimmune disease like RA, the researchers were surprised to see CTAPs associated with structural cells such as fibroblasts and endothelial cells, with relatively few inflammatory leukocytes. They also found that patients’ CTAPs were dynamic and could change over time in response to treatment.&nbsp;</p> <p>Going forward, the researchers aim to expand upon their knowledge of the cell types involved in RA by studying how interconnections between cells promote disease states. Furthermore, they hope this work will encourage increased synovial tissue analysis in RA patients, which is currently not standard practice. While blood tests are more common in RA patients, findings from this study and others emphasize that the cellular profile of synovial tissue differs substantially from that of blood.&nbsp;</p> <p>“What this study shows is that the tissue matters,” said co-senior author Michael Brenner of the Brigham’s Division of Rheumatology, Inflammation and Immunity. “Our findings point to the value of getting synovial tissue biopsies to evaluate the nature of the pathological process, which can be so different across patients. Clinical trials going forward will benefit greatly from assessing tissue characteristics alongside responses to a therapy. By providing this atlas of cell types and pathways involved in RA, we are better able to pursue our precision medicine goal of being able to select the right drug for the right patient and achieve a high response rate.”</p> <p>Co-first authors of the study are Fan Zhang (University of Colorado Anschutz Medical Campus), Anna Helena Jonsson (BWH), Aparna Nathan (Harvard University), and Nghia Millard (BWH). Co-senior authors alongside Raychaudhuri and Brenner are Kevin Wei (BWH), Deepak Rao (BWH), Laura Donlin (Hospital for Special Surgery) and Jennifer Anolik (University of Rochester Medical Center).&nbsp;</p> <p><em>Adapted from <a href="https://www.brighamandwomens.org/about-bwh/newsroom/press-releases-detail?id=4579" target="_blank">a press release issued by Brigham and Women's Hospital</a>.</em></p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported by the Accelerating Medicines Partnership (AMP) in Rheumatoid Arthritis and Lupus Network, a public- private partnership (AbbVie, Arthritis Foundation, Bristol-Myers Squibb Company, Foundation for the National Institutes of Health, GlaxoSmithKline, Janssen Research and Development, Lupus Foundation of America, Lupus Research Alliance, Merck Sharp and Dohme, National Institute of Allergy and Infectious Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Pfizer, Rheumatology Research Foundation, Sanofi and Takeda Pharmaceuticals International). Funding was provided by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the National Human Genome Research Institute.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Zhang F, et al. “Deconstruction of rheumatoid arthritis synovium defines inflammatory subtypes.” <a href="https://www.nature.com/articles/s41586-023-06708-y" target="_blank"><em>Nature</em></a>. Online November 8, 2023.&nbsp;DOI: 10.1038/s41586-023-06708-y.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/medical-and-population-genetics" hreflang="en">Medical and Population Genetics Program</a></div> <div class="field__item"><a href="/broad-tags/immunological-disease" hreflang="en">Immunological Disease</a></div> <div class="field__item"><a href="/broad-tags/transcriptomics" hreflang="en">Transcriptomics</a></div> <div class="field__item"><a href="/broad-tags/single-cell" hreflang="en">Single Cell</a></div> <div class="field__item"><a href="/broad-tags/soumya-raychaudhuri" hreflang="en">Soumya Raychaudhuri</a></div> </div> </div> </div> </div> </div> Thu, 25 Jul 2019 15:44:14 +0000 kzusi@broadinstitute.org 573866 at /news/research-roundup-september-21-2018 <span class="field field--name-title field--type-string field--label-hidden"><h1>Cellular atlas built to guide precision treatment of rheumatoid arthritis</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Tom Ulrich</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2023-11-07T17:33:23-05:00" class="datetime">November 7, 2023</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Cellular atlas built to guide precision treatment of rheumatoid arthritis</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Analysis of more than 314,000 cells from rheumatoid arthritis tissue defines six types of inflammation involving diverse cell types and disease pathways</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Brigham and Women's Hospital Communications </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2023-11-07T17:33:23-05:00" title="Tuesday, November 7, 2023 - 17:33" class="datetime">November 7, 2023</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=FCdaheg0 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=FCdaheg0 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=PwfX1q8e 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="736" height="520"> <source srcset="/files/styles/multiple_ct_header_laptop/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=mw0l5ceY 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="641" height="451"> <source srcset="/files/styles/multiple_ct_header_tablet/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=S5gv7ZlL 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="706" height="417"> <source srcset="/files/styles/multiple_ct_header_phone/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=fkyICH-6 1x" media="all and (max-width: 539px)" type="image/jpeg" width="499" height="294"> <img loading="eager" src="/files/styles/multiple_ct_header_phone/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=fkyICH-6" width="499" height="294" alt="Cartoon illustration of a knee with red concentric circles denoting pain from arthritis" title="Cartoon illustration of a knee with red concentric circles denoting pain from arthritis" typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__description"> </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous"></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/616/feed&amp;title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons__button share-facebook" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/616/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons__button share-x" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&amp;body=/taxonomy/term/616/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons__button share-email" target="_blank" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-with-sidebar text-with-sidebar"> <div class="field field--name-field-sidebar field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-menu sidebar-menu"> <div class="sidebar-menu__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related people</p> </div> <div class="field field--name-field-links field--type-link field--label-hidden field__items"> <div class="field__item"><a href="/bios/soumya-raychaudhuri">Soumya Raychaudhuri</a></div> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-menu sidebar-menu"> <div class="sidebar-menu__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related programs</p> </div> <div class="field field--name-field-links field--type-link field--label-hidden field__items"> <div class="field__item"><a href="/medical-population-genetics">Program in Medical and Population Genetics</a></div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation that leads to pain, joint damage, and disability, which affects approximately 18 million people worldwide. While RA therapies targeted to specific inflammatory pathways have emerged, only some patients’ symptoms improve with treatment, emphasizing the need for multiple treatment approaches tailored to different disease subtypes. To more precisely define cellular drivers of RA, an international research consortium co-led by researchers from the ӳ����ý of MIT and Harvard and Brigham and Women’s Hospital analyzed tissues from RA donors at the single-cell level, integrating multiple forms of analysis to stratify RA by six subtypes of inflammation. The findings, published in <a href="https://www.nature.com/articles/s41586-023-06708-y" target="_blank"><em>Nature</em></a>, shed new light on the variety of cellular causes of RA, which may inform more targeted, effective and patient-tailored therapeutic approaches.</p> <p>“In the treatment of individuals with rheumatoid arthritis, we struggle to find the right treatment for the right patient,” said corresponding author <a href="/node/446111/">Soumya Raychaudhuri</a> of the Brigham’s Division of Rheumatology, Inflammation and Immunity and the ӳ����ý, where he is an institute member in the <a href="/node/8507">Program in Medical and Population Genetics</a>. “We aimed to determine why some subsets of patients don’t respond to conventional treatments by looking at the subtypes of inflammation. We did so from many different angles, using multiple cutting-edge, single-cell techniques and integrating results in a way that hasn’t been done before for an inflammatory disease.”</p> <p>The findings from the study represent a major milestone in the Accelerating Medicines Partnership Rheumatoid Arthritis and Systemic Lupus Erythematosus program, a public-private partnership launched in 2014 to advance molecular- and cellular-level understandings of autoimmune diseases and identify promising drug targets. Through collaboration with researchers and clinicians across the US and UK, the investigators analyzed 79 donor samples of synovial tissue, the inflamed tissue in RA that normally helps cushion and sustain joints. In particular, the researchers examined tissue from patients with new-onset disease and from patients unresponsive to treatment to better identify both the initial drivers of RA as well as those of refractory disease.&nbsp;</p> <p>To “deconstruct” RA pathology on a cellular level, the researchers combined surface protein data and histologic analysis with multiple forms of single-cell RNA-sequencing and bulk RNA sequencing. Despite the variety of methods used to analyze over 314,000 cells, the researchers consistently found evidence of six major types of inflammation, which they stratified by associated cell type, called cell-type abundance phenotypes (CTAPs). While some CTAPS, such as those enriched with T and B cells, were expected finding for an autoimmune disease like RA, the researchers were surprised to see CTAPs associated with structural cells such as fibroblasts and endothelial cells, with relatively few inflammatory leukocytes. They also found that patients’ CTAPs were dynamic and could change over time in response to treatment.&nbsp;</p> <p>Going forward, the researchers aim to expand upon their knowledge of the cell types involved in RA by studying how interconnections between cells promote disease states. Furthermore, they hope this work will encourage increased synovial tissue analysis in RA patients, which is currently not standard practice. While blood tests are more common in RA patients, findings from this study and others emphasize that the cellular profile of synovial tissue differs substantially from that of blood.&nbsp;</p> <p>“What this study shows is that the tissue matters,” said co-senior author Michael Brenner of the Brigham’s Division of Rheumatology, Inflammation and Immunity. “Our findings point to the value of getting synovial tissue biopsies to evaluate the nature of the pathological process, which can be so different across patients. Clinical trials going forward will benefit greatly from assessing tissue characteristics alongside responses to a therapy. By providing this atlas of cell types and pathways involved in RA, we are better able to pursue our precision medicine goal of being able to select the right drug for the right patient and achieve a high response rate.”</p> <p>Co-first authors of the study are Fan Zhang (University of Colorado Anschutz Medical Campus), Anna Helena Jonsson (BWH), Aparna Nathan (Harvard University), and Nghia Millard (BWH). Co-senior authors alongside Raychaudhuri and Brenner are Kevin Wei (BWH), Deepak Rao (BWH), Laura Donlin (Hospital for Special Surgery) and Jennifer Anolik (University of Rochester Medical Center).&nbsp;</p> <p><em>Adapted from <a href="https://www.brighamandwomens.org/about-bwh/newsroom/press-releases-detail?id=4579" target="_blank">a press release issued by Brigham and Women's Hospital</a>.</em></p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported by the Accelerating Medicines Partnership (AMP) in Rheumatoid Arthritis and Lupus Network, a public- private partnership (AbbVie, Arthritis Foundation, Bristol-Myers Squibb Company, Foundation for the National Institutes of Health, GlaxoSmithKline, Janssen Research and Development, Lupus Foundation of America, Lupus Research Alliance, Merck Sharp and Dohme, National Institute of Allergy and Infectious Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Pfizer, Rheumatology Research Foundation, Sanofi and Takeda Pharmaceuticals International). Funding was provided by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the National Human Genome Research Institute.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Zhang F, et al. “Deconstruction of rheumatoid arthritis synovium defines inflammatory subtypes.” <a href="https://www.nature.com/articles/s41586-023-06708-y" target="_blank"><em>Nature</em></a>. Online November 8, 2023.&nbsp;DOI: 10.1038/s41586-023-06708-y.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/medical-and-population-genetics" hreflang="en">Medical and Population Genetics Program</a></div> <div class="field__item"><a href="/broad-tags/immunological-disease" hreflang="en">Immunological Disease</a></div> <div class="field__item"><a href="/broad-tags/transcriptomics" hreflang="en">Transcriptomics</a></div> <div class="field__item"><a href="/broad-tags/single-cell" hreflang="en">Single Cell</a></div> <div class="field__item"><a href="/broad-tags/soumya-raychaudhuri" hreflang="en">Soumya Raychaudhuri</a></div> </div> </div> </div> </div> </div> Fri, 21 Sep 2018 13:42:56 +0000 tulrich@broadinstitute.org 358421 at /news/research-roundup-may-18-2018 <span class="field field--name-title field--type-string field--label-hidden"><h1>Cellular atlas built to guide precision treatment of rheumatoid arthritis</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Tom Ulrich</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2023-11-07T17:33:23-05:00" class="datetime">November 7, 2023</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Cellular atlas built to guide precision treatment of rheumatoid arthritis</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Analysis of more than 314,000 cells from rheumatoid arthritis tissue defines six types of inflammation involving diverse cell types and disease pathways</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Brigham and Women's Hospital Communications </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2023-11-07T17:33:23-05:00" title="Tuesday, November 7, 2023 - 17:33" class="datetime">November 7, 2023</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=FCdaheg0 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=FCdaheg0 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=PwfX1q8e 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="736" height="520"> <source srcset="/files/styles/multiple_ct_header_laptop/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=mw0l5ceY 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="641" height="451"> <source srcset="/files/styles/multiple_ct_header_tablet/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=S5gv7ZlL 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="706" height="417"> <source srcset="/files/styles/multiple_ct_header_phone/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=fkyICH-6 1x" media="all and (max-width: 539px)" type="image/jpeg" width="499" height="294"> <img loading="eager" src="/files/styles/multiple_ct_header_phone/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=fkyICH-6" width="499" height="294" alt="Cartoon illustration of a knee with red concentric circles denoting pain from arthritis" title="Cartoon illustration of a knee with red concentric circles denoting pain from arthritis" typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__description"> </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous"></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/616/feed&amp;title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons__button share-facebook" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/616/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons__button share-x" rel="noopener"> <svg 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field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-menu sidebar-menu"> <div class="sidebar-menu__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related people</p> </div> <div class="field field--name-field-links field--type-link field--label-hidden field__items"> <div class="field__item"><a href="/bios/soumya-raychaudhuri">Soumya Raychaudhuri</a></div> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-menu sidebar-menu"> <div class="sidebar-menu__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related programs</p> </div> <div class="field field--name-field-links field--type-link field--label-hidden field__items"> <div class="field__item"><a href="/medical-population-genetics">Program in Medical and Population Genetics</a></div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation that leads to pain, joint damage, and disability, which affects approximately 18 million people worldwide. While RA therapies targeted to specific inflammatory pathways have emerged, only some patients’ symptoms improve with treatment, emphasizing the need for multiple treatment approaches tailored to different disease subtypes. To more precisely define cellular drivers of RA, an international research consortium co-led by researchers from the ӳ����ý of MIT and Harvard and Brigham and Women’s Hospital analyzed tissues from RA donors at the single-cell level, integrating multiple forms of analysis to stratify RA by six subtypes of inflammation. The findings, published in <a href="https://www.nature.com/articles/s41586-023-06708-y" target="_blank"><em>Nature</em></a>, shed new light on the variety of cellular causes of RA, which may inform more targeted, effective and patient-tailored therapeutic approaches.</p> <p>“In the treatment of individuals with rheumatoid arthritis, we struggle to find the right treatment for the right patient,” said corresponding author <a href="/node/446111/">Soumya Raychaudhuri</a> of the Brigham’s Division of Rheumatology, Inflammation and Immunity and the ӳ����ý, where he is an institute member in the <a href="/node/8507">Program in Medical and Population Genetics</a>. “We aimed to determine why some subsets of patients don’t respond to conventional treatments by looking at the subtypes of inflammation. We did so from many different angles, using multiple cutting-edge, single-cell techniques and integrating results in a way that hasn’t been done before for an inflammatory disease.”</p> <p>The findings from the study represent a major milestone in the Accelerating Medicines Partnership Rheumatoid Arthritis and Systemic Lupus Erythematosus program, a public-private partnership launched in 2014 to advance molecular- and cellular-level understandings of autoimmune diseases and identify promising drug targets. Through collaboration with researchers and clinicians across the US and UK, the investigators analyzed 79 donor samples of synovial tissue, the inflamed tissue in RA that normally helps cushion and sustain joints. In particular, the researchers examined tissue from patients with new-onset disease and from patients unresponsive to treatment to better identify both the initial drivers of RA as well as those of refractory disease.&nbsp;</p> <p>To “deconstruct” RA pathology on a cellular level, the researchers combined surface protein data and histologic analysis with multiple forms of single-cell RNA-sequencing and bulk RNA sequencing. Despite the variety of methods used to analyze over 314,000 cells, the researchers consistently found evidence of six major types of inflammation, which they stratified by associated cell type, called cell-type abundance phenotypes (CTAPs). While some CTAPS, such as those enriched with T and B cells, were expected finding for an autoimmune disease like RA, the researchers were surprised to see CTAPs associated with structural cells such as fibroblasts and endothelial cells, with relatively few inflammatory leukocytes. They also found that patients’ CTAPs were dynamic and could change over time in response to treatment.&nbsp;</p> <p>Going forward, the researchers aim to expand upon their knowledge of the cell types involved in RA by studying how interconnections between cells promote disease states. Furthermore, they hope this work will encourage increased synovial tissue analysis in RA patients, which is currently not standard practice. While blood tests are more common in RA patients, findings from this study and others emphasize that the cellular profile of synovial tissue differs substantially from that of blood.&nbsp;</p> <p>“What this study shows is that the tissue matters,” said co-senior author Michael Brenner of the Brigham’s Division of Rheumatology, Inflammation and Immunity. “Our findings point to the value of getting synovial tissue biopsies to evaluate the nature of the pathological process, which can be so different across patients. Clinical trials going forward will benefit greatly from assessing tissue characteristics alongside responses to a therapy. By providing this atlas of cell types and pathways involved in RA, we are better able to pursue our precision medicine goal of being able to select the right drug for the right patient and achieve a high response rate.”</p> <p>Co-first authors of the study are Fan Zhang (University of Colorado Anschutz Medical Campus), Anna Helena Jonsson (BWH), Aparna Nathan (Harvard University), and Nghia Millard (BWH). Co-senior authors alongside Raychaudhuri and Brenner are Kevin Wei (BWH), Deepak Rao (BWH), Laura Donlin (Hospital for Special Surgery) and Jennifer Anolik (University of Rochester Medical Center).&nbsp;</p> <p><em>Adapted from <a href="https://www.brighamandwomens.org/about-bwh/newsroom/press-releases-detail?id=4579" target="_blank">a press release issued by Brigham and Women's Hospital</a>.</em></p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported by the Accelerating Medicines Partnership (AMP) in Rheumatoid Arthritis and Lupus Network, a public- private partnership (AbbVie, Arthritis Foundation, Bristol-Myers Squibb Company, Foundation for the National Institutes of Health, GlaxoSmithKline, Janssen Research and Development, Lupus Foundation of America, Lupus Research Alliance, Merck Sharp and Dohme, National Institute of Allergy and Infectious Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Pfizer, Rheumatology Research Foundation, Sanofi and Takeda Pharmaceuticals International). Funding was provided by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the National Human Genome Research Institute.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Zhang F, et al. “Deconstruction of rheumatoid arthritis synovium defines inflammatory subtypes.” <a href="https://www.nature.com/articles/s41586-023-06708-y" target="_blank"><em>Nature</em></a>. Online November 8, 2023.&nbsp;DOI: 10.1038/s41586-023-06708-y.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/medical-and-population-genetics" hreflang="en">Medical and Population Genetics Program</a></div> <div class="field__item"><a href="/broad-tags/immunological-disease" hreflang="en">Immunological Disease</a></div> <div class="field__item"><a href="/broad-tags/transcriptomics" hreflang="en">Transcriptomics</a></div> <div class="field__item"><a href="/broad-tags/single-cell" hreflang="en">Single Cell</a></div> <div class="field__item"><a href="/broad-tags/soumya-raychaudhuri" hreflang="en">Soumya Raychaudhuri</a></div> </div> </div> </div> </div> </div> Fri, 18 May 2018 17:15:37 +0000 tulrich@broadinstitute.org 270176 at /blog/whyiscience-qa-yang-luo-uses-math-explore-interplay-between-dna-immune-system-and-disease <span class="field field--name-title field--type-string field--label-hidden"><h1>Cellular atlas built to guide precision treatment of rheumatoid arthritis</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Tom Ulrich</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2023-11-07T17:33:23-05:00" class="datetime">November 7, 2023</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Cellular atlas built to guide precision treatment of rheumatoid arthritis</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Analysis of more than 314,000 cells from rheumatoid arthritis tissue defines six types of inflammation involving diverse cell types and disease pathways</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Brigham and Women's Hospital Communications </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2023-11-07T17:33:23-05:00" title="Tuesday, November 7, 2023 - 17:33" class="datetime">November 7, 2023</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=FCdaheg0 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=FCdaheg0 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=PwfX1q8e 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="736" height="520"> <source srcset="/files/styles/multiple_ct_header_laptop/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=mw0l5ceY 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="641" height="451"> <source srcset="/files/styles/multiple_ct_header_tablet/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=S5gv7ZlL 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="706" height="417"> <source srcset="/files/styles/multiple_ct_header_phone/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=fkyICH-6 1x" media="all and (max-width: 539px)" type="image/jpeg" width="499" height="294"> <img loading="eager" src="/files/styles/multiple_ct_header_phone/public/knee_arthritis_iStock-1279548500_crop.jpeg?itok=fkyICH-6" width="499" height="294" alt="Cartoon illustration of a knee with red concentric circles denoting pain from arthritis" title="Cartoon illustration of a knee with red concentric circles denoting pain from arthritis" typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__description"> </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous"></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/616/feed&amp;title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons__button share-facebook" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/616/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons__button share-x" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&amp;body=/taxonomy/term/616/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons__button share-email" target="_blank" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-with-sidebar text-with-sidebar"> <div class="field field--name-field-sidebar field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-menu sidebar-menu"> <div class="sidebar-menu__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related people</p> </div> <div class="field field--name-field-links field--type-link field--label-hidden field__items"> <div class="field__item"><a href="/bios/soumya-raychaudhuri">Soumya Raychaudhuri</a></div> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-menu sidebar-menu"> <div class="sidebar-menu__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related programs</p> </div> <div class="field field--name-field-links field--type-link field--label-hidden field__items"> <div class="field__item"><a href="/medical-population-genetics">Program in Medical and Population Genetics</a></div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation that leads to pain, joint damage, and disability, which affects approximately 18 million people worldwide. While RA therapies targeted to specific inflammatory pathways have emerged, only some patients’ symptoms improve with treatment, emphasizing the need for multiple treatment approaches tailored to different disease subtypes. To more precisely define cellular drivers of RA, an international research consortium co-led by researchers from the ӳ����ý of MIT and Harvard and Brigham and Women’s Hospital analyzed tissues from RA donors at the single-cell level, integrating multiple forms of analysis to stratify RA by six subtypes of inflammation. The findings, published in <a href="https://www.nature.com/articles/s41586-023-06708-y" target="_blank"><em>Nature</em></a>, shed new light on the variety of cellular causes of RA, which may inform more targeted, effective and patient-tailored therapeutic approaches.</p> <p>“In the treatment of individuals with rheumatoid arthritis, we struggle to find the right treatment for the right patient,” said corresponding author <a href="/node/446111/">Soumya Raychaudhuri</a> of the Brigham’s Division of Rheumatology, Inflammation and Immunity and the ӳ����ý, where he is an institute member in the <a href="/node/8507">Program in Medical and Population Genetics</a>. “We aimed to determine why some subsets of patients don’t respond to conventional treatments by looking at the subtypes of inflammation. We did so from many different angles, using multiple cutting-edge, single-cell techniques and integrating results in a way that hasn’t been done before for an inflammatory disease.”</p> <p>The findings from the study represent a major milestone in the Accelerating Medicines Partnership Rheumatoid Arthritis and Systemic Lupus Erythematosus program, a public-private partnership launched in 2014 to advance molecular- and cellular-level understandings of autoimmune diseases and identify promising drug targets. Through collaboration with researchers and clinicians across the US and UK, the investigators analyzed 79 donor samples of synovial tissue, the inflamed tissue in RA that normally helps cushion and sustain joints. In particular, the researchers examined tissue from patients with new-onset disease and from patients unresponsive to treatment to better identify both the initial drivers of RA as well as those of refractory disease.&nbsp;</p> <p>To “deconstruct” RA pathology on a cellular level, the researchers combined surface protein data and histologic analysis with multiple forms of single-cell RNA-sequencing and bulk RNA sequencing. Despite the variety of methods used to analyze over 314,000 cells, the researchers consistently found evidence of six major types of inflammation, which they stratified by associated cell type, called cell-type abundance phenotypes (CTAPs). While some CTAPS, such as those enriched with T and B cells, were expected finding for an autoimmune disease like RA, the researchers were surprised to see CTAPs associated with structural cells such as fibroblasts and endothelial cells, with relatively few inflammatory leukocytes. They also found that patients’ CTAPs were dynamic and could change over time in response to treatment.&nbsp;</p> <p>Going forward, the researchers aim to expand upon their knowledge of the cell types involved in RA by studying how interconnections between cells promote disease states. Furthermore, they hope this work will encourage increased synovial tissue analysis in RA patients, which is currently not standard practice. While blood tests are more common in RA patients, findings from this study and others emphasize that the cellular profile of synovial tissue differs substantially from that of blood.&nbsp;</p> <p>“What this study shows is that the tissue matters,” said co-senior author Michael Brenner of the Brigham’s Division of Rheumatology, Inflammation and Immunity. “Our findings point to the value of getting synovial tissue biopsies to evaluate the nature of the pathological process, which can be so different across patients. Clinical trials going forward will benefit greatly from assessing tissue characteristics alongside responses to a therapy. By providing this atlas of cell types and pathways involved in RA, we are better able to pursue our precision medicine goal of being able to select the right drug for the right patient and achieve a high response rate.”</p> <p>Co-first authors of the study are Fan Zhang (University of Colorado Anschutz Medical Campus), Anna Helena Jonsson (BWH), Aparna Nathan (Harvard University), and Nghia Millard (BWH). Co-senior authors alongside Raychaudhuri and Brenner are Kevin Wei (BWH), Deepak Rao (BWH), Laura Donlin (Hospital for Special Surgery) and Jennifer Anolik (University of Rochester Medical Center).&nbsp;</p> <p><em>Adapted from <a href="https://www.brighamandwomens.org/about-bwh/newsroom/press-releases-detail?id=4579" target="_blank">a press release issued by Brigham and Women's Hospital</a>.</em></p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported by the Accelerating Medicines Partnership (AMP) in Rheumatoid Arthritis and Lupus Network, a public- private partnership (AbbVie, Arthritis Foundation, Bristol-Myers Squibb Company, Foundation for the National Institutes of Health, GlaxoSmithKline, Janssen Research and Development, Lupus Foundation of America, Lupus Research Alliance, Merck Sharp and Dohme, National Institute of Allergy and Infectious Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Pfizer, Rheumatology Research Foundation, Sanofi and Takeda Pharmaceuticals International). Funding was provided by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the National Human Genome Research Institute.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Zhang F, et al. “Deconstruction of rheumatoid arthritis synovium defines inflammatory subtypes.” <a href="https://www.nature.com/articles/s41586-023-06708-y" target="_blank"><em>Nature</em></a>. Online November 8, 2023.&nbsp;DOI: 10.1038/s41586-023-06708-y.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/medical-and-population-genetics" hreflang="en">Medical and Population Genetics Program</a></div> <div class="field__item"><a href="/broad-tags/immunological-disease" hreflang="en">Immunological Disease</a></div> <div class="field__item"><a href="/broad-tags/transcriptomics" hreflang="en">Transcriptomics</a></div> <div class="field__item"><a href="/broad-tags/single-cell" hreflang="en">Single Cell</a></div> <div class="field__item"><a href="/broad-tags/soumya-raychaudhuri" hreflang="en">Soumya Raychaudhuri</a></div> </div> </div> </div> </div> </div> Thu, 15 Mar 2018 04:05:00 +0000 veronica@broadinstitute.org 226881 at