Role of mRNA and serum soluble cytotoxic T-lymphocyte-associated antigen-4 molecule [sCTLA-4] in systemic lupus erythematosus

ABSTRACT

SLE is a chronic inflammatory systemic autoimmune disease characterised by sustained abnormal immune activation and autoantibody production. A defect in the inhibitory molecules including CTLA-4 is one possibility of the many different mechanisms that may contribute to the pathogenesis. A soluble CTLA-4 protein was found to be present in human serum. The presence of this soluble costimulatory molecule in human serum may provide a means for T-lymphocytes to either enhance or inhibit their biologic effects through additional crossing-linking or competitive blocking to their cell-bound counterparts, thereby influencing the T cell-mediated immune responses. Is to investigate the expression of sCTLA-4 molecule in patients with systemic lupus erythema-tosus [SLE], and correlate its level with disease activity. Thirty-four SLE patients and twelve age- and sex-matched healthy individuals were enrolled in the study. Blood samples from patients and controls were subjected to the following Quantitative detection of sCTLA-4 levels in sera measured by enzyme-linked immunosorbent assay, detection of sCTLA-4 mRNA expression in selected patients and controls detected in their peripheral blood mononuclear cells [PBMCs] by reverse transcriptase-polymerase chain reaction [RT-PCR] method, and detection of CTLA-4 gene polymorphism in promoter region detected by PCR-restriction fragment length polymorphism [RFLP] method. The serum level of sCTLA-4 in the patients with active SLE was statistically much higher than that in the healthy controls and patients not in activity [p<0.001]. The mean intensity of sCTLA-4 mRNA expression was significantly higher in SLE patients when compared to the control group [p<0.001]. There was no statistically significant difference between patients and controls regarding the mean intensity of in CTLA-4 mRNA expression. CTLA-4 gene polymorphism in promoter region at position -318 did not affect levels of sCTLA-4. We couldn't establish a statistically significant difference between patients and controls regarding the frequency of CTLA-4 polymorphism. To exclude the possible effect of corticosteroids on the expression of sCTLA-4, a comparison of sCTLA-4 mRNA as well as serum sCTLA-4 level was done between patients with and without steroid treatment, which revealed no statistically significant difference. Patients with SLE have increased sCTLA-4 expression. However the mechanism and role of increased sCTLA-4 in the pathogenesis of SLE remains tube elucidated