CTLA-4 exon 1 polymorphism in patients with autoimmune blood disorders.

Abstract

CTLA-4 is a CD 28 homologue which plays an important role in negative regulation of T cell response. It’s transit expression on the surface of activated T-cells antagonizes the activating signals and terminates the T-cell response. An A to G polymorphism at position 49 of the CTLA-4 first exon has recently been associated with several autoimmune disorders. In the present study we have examined the prevalence of the A and G alleles of the CTLA-4 gene in 110 patients with autoimmune blood diseases, including 50 patients with autoimmune hemolytic anemia (20 patients with idiopathic AIHA and 30 patients with AIHA and CLL) and 60 patients with ITP. Control subjects were 100 healthy individuals and 100 CLL patients without clinical evidence for an autoimmune disease. Overall, the G allele was significantly more frequent among the patients with autoimmune disorders (p=0.016). However, this was entirely due to the higher prevalence of the G allele among patients with AIHA (p=0.003), whereas no difference was observed between patients with ITP and controls. The correlation between the CTLA-4 G allele and the development of AIHA was most significant when we compared only patients with CLL (p=0.004), and was lower when the comparison was done between DAT positive and DAT negative CLL patients, regardless of the presence of AIHA (p=0.021). The obtained data indicate that the G allele of CTLA-4 may predispose to the development of AIHA, possibly through the amplification of a prexisting autoimmune response.