Abstract
Background: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disorder characterised by persistent synovial inflammation and progressive joint destruction. The immunomodulatory roles of IL-40, IL-37, and IL-38 in RA remain incompletely understood, particularly in Middle Eastern patient populations. Research question: Are serum levels of IL-40, IL-37, and IL-38 elevated in RA patients compared with healthy controls, and do they correlate with established pro-inflammatory markers? Methods: A cross-sectional comparative study was conducted at Tikrit Teaching Hospital, Salah al-Din, Iraq (January–September 2025), enrolling 60 RA patients and 30 age- and sex-matched healthy controls. Serum cytokines were quantified by ELISA. Normality was assessed by the Shapiro-Wilk test; Mann-Whitney U and Spearman rank correlation were applied. Results: IL-40 (8.91±1.08 vs 7.29±2.24 pg/mL; p=0.0002), IL-37 (398.44±72.95 vs 68.33±29.30 pg/mL; p<0.001), and IL-38 (635.48±197.43 vs 145.23±56.17 pg/mL; p<0.001) were all significantly elevated in RA. All pro-inflammatory markers were markedly elevated (p<0.001). Within the RA group, IL-37 correlated positively with CRP (r=0.352, r²=0.124, p=0.006) and ESR (r=0.311, r²=0.097, p=0.016). Conclusion: These findings suggest that IL-40, IL-37, and IL-38 may be actively involved in RA immunopathology. The moderate positive correlations between IL-37 and acute-phase reactants may reflect a counter-regulatory response proportional to systemic inflammatory burden. Confirmation in larger, longitudinal, multi-centre studies is required.
Keywords
Rheumatoid arthritis; IL-40; IL-37; IL-38; Pro-inflammatory cytokines; Iraq; Cross-sectional study