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Davis Initiative in Rheumatoid Arthritis Researchion and Research"},{"name":"Mark E. and Mary A. Davis Initiative in Rheumatoid Arthritis Research"}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2026,4,3]]},"abstract":"<jats:p>\n                    The underlying immunopathogenesis of inflammatory arthritis (IA) immune-related adverse event (irAE) remains obscure. Unlike rheumatoid arthritis (RA), where autoantibodies and B cell dysfunction are central features, the contribution of humoral immunity to IA-irAE is unclear. Here, we performed immunophenotyping of peripheral blood from patients with IA-irAE and compared them with patients with seronegative RA, immune checkpoint inhibition\u2013treated patients without irAE, and healthy controls. IA-irAE was marked with increased cytotoxic gene expression and metabolic activation in T cells and reduced CXCR3 and CCR6 expression in CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells. Contrary to seronegative RA, patients with IA-irAE displayed no substantial elevation in autoantibody levels or atypical CD11c\n                    <jats:sup>+<\/jats:sup>\n                    CD21\n                    <jats:sup>\u2212<\/jats:sup>\n                    B cells. IA-irAE was further characterized by elevated levels of interleukin-6 (IL-6), IL-12, and type I interferon, which correlated with the T cell activation phenotypes. Together, our findings define IA-irAE as a disease with certain immunological features distinctive from RA, representing a potentially T cell\u2013driven, autoantibody-independent autoimmunity. These results offer insights into immune tolerance breakdown and therapeutic targeting in irAEs.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aea4262","type":"journal-article","created":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T17:58:42Z","timestamp":1775066322000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":3,"title":["Inflammatory arthritis irAE may represent a unique autoimmune disease primarily driven by T cells but likely not autoantibodies"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8411-319X","authenticated-orcid":true,"given":"Xingxing","family":"Zhu","sequence":"first","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, Mayo Clinic, Rochester, MN, 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