Clinical significance of serum TNFalpha and -308 G/A promoter polymorphism and serum Il-6 and -174 G/C promoter polymorphism in systemic lupus erythematosus patients

ABSTRACT

Systemic lupus erythematosus [SLE] is a disorder of immune regulation where cytokine imbalance and genetic factors are implicated in its pathogenesis. To evaluate the clinical significance of serum levels of tumor necrosis factor alpha [TNFalpha] and its -308 G/A promoter polymorphism as well as the IL-6 and -174 promoter polymorphism in SLE patients and find any association to the clinical and laboratory features as well as to the disease activity and severity. We studied 37 female SLE patients and age and gender matched healthy control. Demographic, clinical and serological data were evaluated and the Systemic Lupus Erythematosus Disease Activity Index [SLEDAI] and the Systemic Lupus International Collaboration Clinics/ACR Damage Index [SLICC] were assessed. Serum TNF-alpha and IL-6 levels were measured using enzyme-linked immunosorbent assay [ELISA] and DNA genotyped for TNF-alpha promoter [-308 G/A] and IL-6 promoter [-174 G/C] by polymerase-chain reaction-restriction fragment-length polymorphism [PCR-RFLP] analysis. Serum TNF-alpha and IL-6 levels were significantly higher in the SLE patients compared to control. Regarding IL-6, there was a statistically significant difference between the levels in the three groups according to the promoter polymorphisms. Patients with constitutional symptoms showed higher level of IL-6 while the TNF-alpha level was significantly lower in those with pulmonary manifestations. There was a tendency to a higher TNF-alpha and IL-6 level in those with neuropsychiatric manifestations. Serum TNF-alpha, -308 G/A promoter polymorphism, IL-6 and -174 G/C were higher in SLE patients than in healthy controls. To confirm our results we propose that larger scale, multicenter studies with longer evaluation periods are needed