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.