Interleukin-18 gene polymorphisms in systemic lupus erythematosus: relation to disease status.

ABSTRACT

Systemic lupus erythematosus (SLE) is a multisystem autoimmune connective tissue disorder characterized by loss of self-tolerance causing immune-mediated tissue destruction and various clinical presentations Interleukin-18 (IL-18) is a proinflammatory cytokine that plays an important role in chronic inflammation and autoimmune disorders. This study investigates polymorphisms of the IL-18 gene in SLE patients at positions -607 and -137 of the promoter to elucidate their possible roles in the activity and severity of this disease. Fifty SLE patients and fifty unrelated healthy control group were included. AII SLE patients underwent thorough clinical examination and SLE disease activity assessment using SLEDAI. Genomic DNA was extracted from peripheral venous blood. Sequence-specific primer PCR analysis were used to genotype the DNA samples for SNP-607and SNP-137, while plasma IL-18 concentrations of patients and control subjects were measured by enzyme-linked immunosorbent assay. The frequency of SNP-607/CC genotype showed significant increase (P < 0.05), while genotype SNP-607/CA showed significant decrease (P < 0.05) in SLE patients as compared to the control group. Significantly elevated levels of plasma IL-18 were found in patients compared to controls (P < 0.001) and those with genotype CC at -607 demonstrated the highest IL-18 level (331.74 +/- 36.48 pg/mL). Serum IL-18 levels showed significant positive correlations with the ESR 1st hr. (r = 0.89), protein/creatinine ratios (r = 0.88), anti-dsDNA titers (r = 0.44) and SLEDAI scores (r = 0.91). In contrast, significant negative correlations were found with HB% r = -0.68, creatinine clearance (r = -0.87) and C3 (r = -0.81). In addition, a statistically significant association was found between IL-18 of CC -607 genotype and lupus nephritis, arthritis and immunological disorders. In conclusion, IL-18 promoter gene polymorphisms at position -607 may contribute to SLE activity and accelerate SLE development by enhancing production of IL-18 protein in SLE patients.