{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T03:29:43Z","timestamp":1792553383700,"version":"4.5.0"},"reference-count":42,"publisher":"American Society for Clinical Investigation","issue":"12","license":[{"start":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T00:00:00Z","timestamp":1718582400000},"content-version":"vor","delay-in-days":48,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012041","name":"Versus Arthritis","doi-asserted-by":"crossref","award":["22440"],"award-info":[{"award-number":["22440"]}],"id":[{"id":"10.13039\/501100012041","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,6,17]]},"abstract":"<jats:p>\n                    Ectopic lymphoid structures (ELSs) in the rheumatoid synovial joints sustain autoreactivity against locally expressed autoantigens. We recently identified recombinant monoclonal antibodies (RA-rmAbs) derived from single, locally differentiated rheumatoid arthritis (RA) synovial B cells, which specifically recognize fibroblast-like synoviocytes (FLSs). Here, we aimed to identify the specificity of FLS-derived autoantigens fueling local autoimmunity and the functional role of anti-FLS antibodies in promoting chronic inflammation. A subset of anti-FLS RA-rmAbs reacting with a 60 kDa band from FLS extracts demonstrated specificity for HSP60 and partial cross-reactivity to other stromal autoantigens (i.e., calreticulin\/vimentin) but not to citrullinated fibrinogen. Anti-FLS RA-rmAbs, but not anti\u2013neutrophil extracellular traps rmAbs, exhibited pathogenic properties in a mouse model of collagen-induced arthritis. In patients, anti-HSP60 antibodies were preferentially detected in RA versus osteoarthritis (OA) synovial fluid. Synovial\n                    <jats:italic>HSPD1<\/jats:italic>\n                    and\n                    <jats:italic>CALR<\/jats:italic>\n                    gene expression analyzed using bulk RNA-Seq and GeoMx-DSP closely correlated with the lympho-myeloid RA pathotype, and HSP60 protein expression was predominantly observed around ELS. Moreover, we observed a significant reduction in synovial HSP60 gene expression followed B cell depletion with rituximab that was strongly associated with the treatment response. Overall, we report that synovial stromal-derived autoantigens are targeted by pathogenic autoantibodies and are associated with specific RA pathotypes, with potential value for patient stratification and as predictors of the response to B cell\u2013depleting therapies.\n                  <\/jats:p>","DOI":"10.1172\/jci169754","type":"journal-article","created":{"date-parts":[[2024,6,16]],"date-time":"2024-06-16T14:00:39Z","timestamp":1718546439000},"source":"Crossref","is-referenced-by-count":21,"title":["Autoimmunity to stromal-derived autoantigens in rheumatoid ectopic germinal centers exacerbates arthritis and affects clinical response"],"prefix":"10.1172","volume":"134","author":[{"given":"Elisa","family":"Corsiero","sequence":"first","affiliation":[{"name":"Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London (QMUL), London, United 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