Citations 2
Inflammatory arthritis irAE may represent a unique autoimmune disease primarily driven by T cells but likely not autoantibodies
Zhu, Xingxing, Yu, Yue , Chen, S., Langenfeld, Hannah E., Li, Yanfeng , Wang, Panwen , McCabe, Chantal E. , Hanson, Andrew C. , Sharp, Brenna , Woltzen, Amber, Markovic, Svetomir N. , Davis, John M., Dong, H. C., Crowson, Cynthia S., Thanarajasingam, Uma , Zeng, Hu, Dong, Haidong , Davis, John M. , Zeng, Hu , Zhu, Xingxing , Li, Ying , Zhu, Xingxing , Chen, Shiju, McCabe, Chantal , Hanson, Andrew C , Sharp, Brenna E, Woltzen, Amber , Markovic, Svetomir , Davis, John M , Dong, Haidong , Crowson, CS , Thanarajasingam, Uma , Zeng, Hu , Li, Ying , Li, Ying, Crowson, Cynthia S.
Science Advances | April 1, 2026 | Volume: 12 | Issue: 14 | Pages: No page available
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.
The association of osteoarthritis with the risk of de novo inflammatory arthritis in patients receiving immune checkpoint inhibitors: a retrospective study
Chen, S., Zhu, Xingxing, Zhang, Zhiqiang, Thanarajasingam, Uma , Crowson, Cynthia S, Zeng, Hu, Zeng, Hu , Zhu, Xingxing , Chen, Shiju, Zhu, Xingxing , Zeng, Hu , Crowson, Cynthia S.
No container title available | January 30, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available
ABSTRACT Objective Identifying risk factors enables stratification of patients’ susceptibility to inflammatory arthritis immune-related adverse events (IA-irAE). This retrospective study examines whether preexisting osteoarthritis (OA) increases the likelihood of de novo IA in patients treated with immune checkpoint inhibitors (ICIs). Methods The prevalence of OA among ICI–treated patients who developed IA-irAE, those who developed other types of irAEs but not IA (non-IA irAE), and those who did not develop any irAEs (non-irAE) were compared. Electronic medical records were reviewed to extract demographic, clinical and laboratory data. Group comparisons and logistic regression analyses were performed. Results 181 de novo IA-irAE patients, 140 non-IA irAE patients and 170 non-irAE patients were included. The prevalence of OA was significantly higher in the IA-irAE group (69%) than the non-IA irAE group (48%) and the non-irAE group (48%) (both p < 0.001). The IA-irAE group demonstrated a higher frequency of multisite OA, with predominant hand involvement (62%) than the non-IA irAE with OA group (13%) and the non-irAE with OA group (13%) (both p < 0.001). A family history of autoimmune disease (AID) (OR 2.03, 95% CI 1.02–4.05), preexisting OA (OR 2.88, 95% CI 1.85–4.52) and melanoma (OR 2.63, 95% CI 1.56–4.47) were identified as risk factors for the development of IA-irAE. Conclusions OA was more prevalent among ICI-treated patients developing IA-irAE than those who did not. Hand OA was the most common OA pattern in IA-irAE patients. Preexisting OA, melanoma and a family history of AID were risk factors for IA-irAE.