CD28, CTLA-4 and CCL5 gene polymorphisms in patients with rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint destruction caused by infiltrating leukocytes including T cells. An important role in T cell co-stimulation is played by the CD28, as a stimulatory signal transducer and the inhibitory CTLA-4. CCL5 is produced by circulating T cells and plays an active role in the chemotactic activity of T cells in RA. The aim of this study was to examine the associations between polymorphisms within CD28, CTLA-4, and CCL5 genes and RA. We examined 422 patients (340 female, 82 male, mean age 57.5 ± 12.5 years) with rheumatoid arthritis and 338 healthy subjects (261 female, 77 male). Disease activity was determined on the basis of DAS28 score. The patients with DAS28 of ≤2.5 were classified as subjects in remission of disease symptoms; the patients who had DAS28 of >2.5 were classified as subjects with active form of RA. There were no statistically significant differences in the distribution of studied genotypes and alleles between RA patients and the control group. A statistically significant difference was observed in the distribution of CTLA4 exon 1 +49A>G rs231775 genotypes between patients with DAS28 ≤ 2.5 and DAS28 > 2.5 where the increased frequency of AA genotype among patients with DAS28 > 2.5 was revealed (OR 1.55; 95% CI 1.01-2.38). The results of our study suggest no significant association between CD28 rs1980422, CCL5 rs2107538, CTLA-4 exon 1 +49A>G rs231775 and rs3087243 gene polymorphisms and RA in the Polish population. Our results indicate a possible association between CTLA-4 exon 1 +49A>G rs231775 gene polymorphism and RA activity.