Role of TNFα and IL-10 in rheumatoid arthritis and association with some HLA II DR and DQ alleles

Rheumatoid arthritis (RA) is a systemic disease that causes progressive joint damage and disability. The affected tissues are histologicaly characterized by prominent infiltration with inflammatory mononuclear cells, such as T cells and macrophages, and proliferation of synovial fibroblasts. Inflammatory cytokines, including tumor necrosis factor (TNF), and IL-6, which are mainly produced by macrophages, play a central role in the development of synoviitis. For example, TNF is shown to directly induce synovial fibroblast proliferation, which leads to the pannus formation. TNF is also critical for the expression of inflammatory chemokines and adhesion molecules, which, in combination, facilitate further leukocyte attraction and perpetuation of inflammatory responses. In addition to environmental factors, genetic constitution of host organism seems to play a crucial role in acquiring and development of the disease. The present study was carried out to investigate the association of HLA-class 11 (DR, DQ) with RA disease by genotyping in Iraqi patients, as well as to provide information about genotypes that confer susceptibility or resistance to this disease. Aim of the study was to assess the role, strength and profile of immune response in patients with rheumatoid arthritis by estimation of TNFα, IL-10 and levels, as compared to healthy control group, and to identify a role for certain alleles in occurrence of the disease. The 5-ml samples of venous blood were taken from 30 patients suffering from confirmed rheumatoid arthritis, 19 patients were females and 11 males, as well 30 healthy control samples were enrolled in this study. All the samples were subjected to ELISA test, in order to estimate TNFα, and IL-10 levels in serum from 3 ml of blood. DNA was extracted from 2 ml of blood, and HLA-Class Il genotyping was performed by polymerase chain reaction-sequence specific oligonucleotide probes (PCR-SSO). A highly statistical significant variation, both in TNFα, and IL-10 levels between RA patients group and healthy control group was observed (p < 0.001). No statically significant differences between males and females in frequency of the RA (p = 0.119). HLA-class II genotyping of RA patients in comparison with healthy control showed significant differences in some alleles between the both groups. Some DR alleles proved to be informative, e.g., the DR*0403 allele showed a significantly increased frequency in control group with 35%, compared with 6.67% in RA group (p = 0.02). The DR*701 allele showed increased frequency in the patients with 9 cases (30%, p = 0.007). Genotyping of DQ alleles did not any no significant differences. Although *0202 allele occurred in 40% of patients group versus 15% in control groups, it was not significant (p > 0.05).

rheumatoid arthritis, TNFα, IL-10, HLA genotyping, allele frequency

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