R OLE OF TNF-α AND IL-10 IN RHEUMATOID ARTHRITIS DISEASE AND THE ASSOCIATION WITH SOME HLA-11 DR AND DQ ALLELES

Abstract

Background: Rheumatoid arthritis (RA) is a systemic disease that causes progressive joint damage and disability. Inflammatory cytokines, including tumor necrosis factor (TNF), and IL-6, which are mainly produced by macrophages, play a central role in the development of synovitis. For example, TNF play major role in the expression of adhesion molecules and inflammatory chemokines which, in combination, facilitate increase inflammatory leukocytes and severe inflammatory responses. In addition to environmental factors, genetic constitution of hosts seems to play a crucial role in acquiring the disease and its development. The current study was carried out for the detection of any association of HLA-class 11 (DR, DQ) with RA disease by genotyping in Iraqi patients, as well as to provide information about genotypes that may confer susceptibility or resistance to the development of the disease. Aim of the study: to assess the role, strength and profile of immune response in patients with rheumatoid arthritis by estimation of TNFα, IL-10 and levels in compare to healthy control group. And to identify any role for certain alleles in exposure to the disease. Material and Method: Five ml of venous blood samples withdrawn from 30 patients suffering from confirmed Rheumatoid arthritis disease, 19 patients were females and 11 males in addition to 30 healthy control samples were enrolled in this study all samples were subjected for (ELISA test) (Enzyme Linked Immunosorbent assay) to estimate the TNFα, and IL-10 Levels by using the three ml of blood to extract the serum. Another two ml was used for DNA extraction, and then HLA-Class Il genotyping was performed by polymerase chain reaction-sequence specific oligonucleotide probes (PCR-SSO). Results: A highly statistically significant variation both in TNF – α levels, and IL-10 between RA patients group and healthy control group was observed, the P value was <0.001 No statically significant differences between males and females in frequency of the RA with 0.119 P value. HLA-class II genotyping of RA patients in compare with healthy control reflect significant differences in some alleles. Among DR alleles there were some alleles showed higher frequency in control group; DR*0403 allele showed increase frequency in control groups with 35% compared with 6.67% in patients group, and the P value was 0.020, which is considered as statistically significant Another DR*701 allele showed increase frequency in patients groups with 9 cases 30% and the P value was 0.007. Concerning DQ allele’s genotyping no significant allele’s frequency was noticed. Although *0202 allele occurred in 40% of patients group and 15% in control groups it was not significant statistically as the P value was more than 0.05