Citations 1
Inflammatory arthritis irAE may represent a unique autoimmune disease primarily driven by T cells but likely not autoantibodies
Zhu, Xingxing, Yu, Yue , Chen, S., Langenfeld, Hannah E., Li, Yanfeng , Wang, Panwen , McCabe, Chantal E. , Hanson, Andrew C. , Sharp, Brenna , Woltzen, Amber, Markovic, Svetomir N. , Davis, John M., Dong, H. C., Crowson, Cynthia S., Thanarajasingam, Uma , Zeng, Hu, Dong, Haidong , Davis, John M. , Zeng, Hu , Zhu, Xingxing , Li, Ying , Zhu, Xingxing , Chen, Shiju, McCabe, Chantal , Hanson, Andrew C , Sharp, Brenna E, Woltzen, Amber , Markovic, Svetomir , Davis, John M , Dong, Haidong , Crowson, CS , Thanarajasingam, Uma , Zeng, Hu , Li, Ying , Li, Ying, Crowson, Cynthia S.
Science Advances | April 1, 2026 | Volume: 12 | Issue: 14 | Pages: No page available
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–treated 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 + T cells. Contrary to seronegative RA, patients with IA-irAE displayed no substantial elevation in autoantibody levels or atypical CD11c + CD21 − 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–driven, autoantibody-independent autoimmunity. These results offer insights into immune tolerance breakdown and therapeutic targeting in irAEs.