Inflammatory arthritis immune related adverse events represent a unique autoimmune disease entity primarily driven by T cells, but likely not autoantibodies

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 in-depth immunophenotyping of peripheral blood from patients with IA irAE, and compared them with seronegative RA patients, ICI-treated patients without irAE, and healthy controls.

IA irAE was marked by a distinct T cell-dominated profile, with CD4+ T cells exhibiting reduced CXCR3 and CCR6 expression, and both CD4+ and CD8+ T cells showing increased cytotoxic molecule expression and metabolic activation. In contrast 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 a proinflammatory cytokine milieu, with elevated levels of IL-6, IL-12, and type I IFN, which correlated with the observed T cell activation phenotypes.