Diagnostic and monitoring value of serum interleukin-33 and rs16924159 polymorphism in relation to disease activity and tumor necrosis factor inhibitor response in rheumatoid arthritis.

Objective: This study aimed to establish the diagnostic and monitoring value of serum interleukin-33 (IL-33) levels and IL-33 rs16924159 polymorphism regarding disease activity and response to tumor necrosis factor (TNF) inhibitors in rheumatoid arthritis (RA) patients.

Methods: In a case-control study, 100 RA patients and 100 healthy individuals were enrolled. We intentionally sampled 50 responders and 50 non-responders after 6 months of TNF inhibitors. Serum IL-33 levels were determined by using enzyme-linked immunosorbent assay (ELISA). Rs16924159 genotyping was performed using TaqMan real-time polymerase chain reaction. Disease activity was evaluated by the clinical disease activity index (CDAI), and treatment response was evaluated after 6 months of TNF inhibitor therapy.

Results: IL-33 was markedly elevated in RA patients compared to controls (p<0.001), and IL-33 possessed satisfactory diagnostic accuracy area under the curve (AUC)=0.810 (95% confidence interval [CI]=0.747~0.872, p<0.001). Homozygous mutant AA genotype of rs16924159 was associated with higher disease activity (p<0.001) and poorer response to TNF inhibitors (odds ratio=5.26, 95% CI=1.07~25.77, p=0.040). Non-responders were found to have more elevated serum levels of IL-33 compared to responders (p<0.001). Serum IL-33 levels (p=0.015) and rs16924159 genotype (p<0.001) were significantly associated with CDAI scores.

Conclusion: Elevated IL-33 and the rs16924159 polymorphism were associated with higher RA disease activity and lower 6 month TNF inhibitor response in this cohort. IL-33 showed moderate diagnostic performance (AUC=0.81, sensitivity=66%, specificity=92%), and routine clinical use-especially to guide personalized treatment-requires external validation in independent cohorts and prospective, comparative studies.