Cytotoxic T lymphocyte antigen 4 (CTLA-4) dimorphism in patients with systemic lupus erythematosus

Objective Genetic susceptibility to systemic lupus erythematosus (SLE) is conferred n ot only by various genes within the major histocompatibility complex (MHC) region, but also by several other non-MHC linked genes. The negatively sign alling molecule CTLA-4 is involved in establishing and maintaining of perip heral T cell tolerance which controls T cell activation and reactivity. Its attenuating action helps to prevent an inappropriate initiation of T cell responses to self antigens and to terminate ongoing T cell responses, We te sted if there was an association between CTLA-4 and SLE, a disease with B a nd T cell hyperreactivity and impaired peripheral T cell tolerance Methods Using the polymerase chain reaction restriction fragment length polymorphis m method with Bbv I digestion, we assessed an exon I transition dimorphism (49 A/G) of the CTLA-4 gene in 102 SLE patients and in 76 healthy controls. Results The distribution of CTLA -4 exon 1 genotypes in the SLE group was significa ntly different from that in the controls (chi(2) = 6.178, p < 0.05). 17.6% of the SLE patients were G/G homozygotes compared to 5.3% of the controls; 36.3% were A/G heterozygotes vs 40.8% of controls; and 46.1% were A/A homoz ygotes vs 53.9% of the controls. The frequency of the G allele was signific antly higher in SLE patients (35.8%) than in controls (25.7%; chi(2) = 4.14 2, p = 0.042). Conclusion Our results indicate that the non-MHC linked CTLA-4 gene could confer susce ptibility in SLE, as it does in various other autoimmune diseases (Hashimot o thyroiditis, Graves' disease, IDDM).