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

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.