{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T05:41:29Z","timestamp":1793166089724,"version":"4.5.0"},"reference-count":95,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"668","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2022,10,26]]},"abstract":"<jats:p>\n                    The mucosal origins hypothesis of rheumatoid arthritis (RA) proposes a central role for mucosal immune responses in the initiation or perpetuation of the systemic autoimmunity that occurs with disease. However, the connection between the mucosa and systemic autoimmunity in RA remains unclear. Using dual immunoglobulin A (IgA) and IgG family plasmablast\u2013derived monoclonal autoantibodies obtained from peripheral blood of individuals at risk for RA, we identified cross-reactivity between RA-relevant autoantigens and bacterial taxa in the closely related families\n                    <jats:italic>Lachnospiraceae<\/jats:italic>\n                    and\n                    <jats:italic>Ruminococcaceae<\/jats:italic>\n                    . After generating bacterial isolates within the\n                    <jats:italic>Lachnospiraceae\/Ruminococcaceae<\/jats:italic>\n                    genus\n                    <jats:italic>Subdoligranulum<\/jats:italic>\n                    from the feces of an individual, we confirmed monoclonal antibody binding and CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell activation in individuals with RA compared to control individuals. In addition, when\n                    <jats:italic>Subdoligranulum<\/jats:italic>\n                    isolate 7 but not isolate 1 colonized germ-free mice, it stimulated T\n                    <jats:sub>H<\/jats:sub>\n                    17 cell expansion, serum RA\u2013relevant IgG autoantibodies, and joint swelling reminiscent of early RA, with histopathology characterized by antibody deposition and complement activation. Systemic immune responses were likely due to mucosal invasion along with the generation of colon-isolated lymphoid follicles driving increased fecal and serum IgA by isolate 7, because B and CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell depletion not only halted intestinal immune responses but also eliminated detectable clinical disease. In aggregate, these findings demonstrate a mechanism of RA pathogenesis through which a specific intestinal strain of bacteria can drive systemic autoantibody generation and joint-centered antibody deposition and immune activation.\n                  <\/jats:p>","DOI":"10.1126\/scitranslmed.abn5166","type":"journal-article","created":{"date-parts":[[2022,10,26]],"date-time":"2022-10-26T13:58:45Z","timestamp":1666792725000},"source":"Crossref","is-referenced-by-count":162,"title":["Clonal IgA and IgG autoantibodies from individuals at risk for rheumatoid arthritis identify an arthritogenic strain of\n                    <i>Subdoligranulum<\/i>"],"prefix":"10.1126","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6617-8747","authenticated-orcid":true,"given":"Meagan E.","family":"Chriswell","sequence":"first","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam R.","family":"Lefferts","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1659-8927","authenticated-orcid":true,"given":"Michael R.","family":"Clay","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7032-9280","authenticated-orcid":true,"given":"Alex Ren","family":"Hsu","sequence":"additional","affiliation":[{"name":"Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5851-7246","authenticated-orcid":true,"given":"Jennifer","family":"Seifert","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie L.","family":"Feser","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cliff","family":"Rims","sequence":"additional","affiliation":[{"name":"Benaroya Research Institute, Seattle, WA 98101, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle S.","family":"Bloom","sequence":"additional","affiliation":[{"name":"Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3556-3175","authenticated-orcid":true,"given":"Elizabeth A.","family":"Bemis","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sucai","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1798-7510","authenticated-orcid":true,"given":"Megan D.","family":"Maerz","sequence":"additional","affiliation":[{"name":"Benaroya Research Institute, Seattle, WA 98101, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6669-228X","authenticated-orcid":true,"given":"Daniel N.","family":"Frank","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2563-5155","authenticated-orcid":true,"given":"M. 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