Determination of the CTLA-4 gene polymorphism by PCR-RFLP method in systemic Lupus erythematozus patients

ABSTRACTSystemic lupus erythematosus (SLE) is a chronic, inflammatory andmultisystemic autoimmune disease characterized by many cellular andhumoral immunological abnormalities. Inappropriate, T cell dependent,expansion of autoreactive B cells is considered to play a role in theproduction of pathogenic autoantibodies.Two signals are required for T cell activation. The first signal is fromT cell receptor (TCR) and the second is from co-stimulatory moleculesknown as secondary stimulatory molecules. CD28 is a co-stimulatorymolecule. It binds to CD80/CD86 on antigen-presenting cells and producethe signal to activate the T cell. Therefore, it is also called positiveregulatory molecule. Cytotoxic T lymphocyte associated antigen 4 (CTLA-4)is also a co-stimulator molecule and homologous to CD28. CTLA-4 interactwith CD80 /CD86 on antigen presenting cell (APC) like CD28. On thecontrary the CD28, CTLA-4 is a molecule produces which inhibitory signals.Hence it plays an important role in development of peripheral tolerance.CD28 and CTLA-4 molecules regulate immune response against self andnon -self antigens by contrary activation of antigen specific T cells.2q33 region is susceptibility loci for human SLE and CTLA-4molecule is placed in this region. Because of showing inhibitory effect on Tcell activation CTLA-4 molecule is a candidate gene, which may predisposeto SLE disease.CTLA-4 plays an important role in regulating T cell activation andmay help to limit T cell response under inflammatory conditions. Geneticvariation in CTLA-4 causes many autoimmune diseases. It is reported thatExon I (+49 A/G) dimorphism, one of the polymorphisms in this gene,increases the disease sensitivity in Japanese population. Unfortunately insome population like Chinese no relationship between this polymorphismand SLE have been described. In this study we aimed to detect whetherthere is any relationship between CTLA-4 Exon I (+49 A/G) polymorphismand SLE disease and its activitation in Turkish population.Key words: SLE, CTLA-4, PCR-RFLP, exon I +49 A/G,polymorphism, co-stimulatory moleculesv