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

Zhu, Xingxing1; Yu, Yue1; Chen, Shiju1; Langenfeld, Hannah1; Li, Yanfeng1; Wang, Panwen1; Li, Ying1; McCabe, Chantal1; Hanson, Andrew1; Sharp, Brenna1; Woltzen, Amber1; Markovic, Svetomir1; Davis, John1; Dong, Haidong1; Crowson, Cynthia1; Thanarajasingam, Uma1; Zeng, Hu1

Published Mar 17, 2026 on Dryad. https://doi.org/10.5061/dryad.fxpnvx167

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Abstract

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 IA-irAE patients and compared them with seronegative RA patients, ICI-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, IA-irAE patients displayed no significant elevation in autoantibody levels or atypical CD11c⁺CD21⁻ B cells. IA-irAE was further characterized by elevated levels of IL-6, IL-12, and type I IFN, which correlated with the T cell activation phenotypes. Altogether, 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.