Research Associate Mayo Clin. Col. of Med. and Sci. Rochester, MN, Minnesota, United States
Disclosure(s):
Xingxing Zhu, PhD: No financial relationships to disclose
Introduction/Rationale: 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.
Methods: 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.
Results: 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.
Conclusion: 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.
