Inflammatory arthritis irAE may represent a unique autoimmune disease primarily driven by T cells but likely not autoantibodies

作者：Xingxing Zhu, Yue Yu, S. Chen, Hannah E. Langenfeld, Yanfeng Li, Panwen Wang, Yan Li, Chantal E. McCabe, Andrew C. Hanson, Brenna Sharp, Amber Woltzen, Svetomir N. Markovic, John M. Davis, H. C. Dong, Cynthia S. Crowson, Uma Thanarajasingam, Hu Zeng · 发表于：Science Advances · 年份：2026 · DOI：10.1126/sciadv.aea4262 · 被引用次数：1 · 研究领域：Rheumatoid Arthritis Research and Therapies、Cancer Immunotherapy and Biomarkers、T-cell and B-cell Immunology

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.