| Rheumatoid arthritis(RA) is a kind of common chronic inflammatory arthritis.The aetiology is unknown but the disease is postulated to result from the interaction with immune genetic and environmental factors. Of all the factors, a large component of genetic risk associated with disease susceptibility to rheumatoid arthritis can be attributed to the human leukocyte antigen (HLA) locus on chromosome 6p21.With this locus,the strongest genetic association is with the major histocompatibility complex (MHC) Class II antigen HLA-DR4 gene,which account for these disease associations have been identified.There is clinical utility in analysis of patients with early polyarthritis ,HLA-DR4 can be assessed for the likelihood of progression to severe erosive RA.HLA-DR4 in RA is to influence the types of antigens recognized by immune T cells,The HLA DR genes encode MHC class II molecules,which are dimeric proteins that bind antigenic peptides for presentation to lymphocytes and then the autoreactive T-cells are activitied and amplified.As a result the RA is triggered and developed. There is an imbalance of TH1/TH2 cytokine production in the patients with RA ,moreover it correlates well with disease activity . In this paper the method of DNA amplification with PCR was used to dertermine HLA-DR4 allels.,the serum lever of INF-gamma, IL-4(the secreted pattern of TH1, TH2 cytokines) were mearsured by enzyme linked immunosorbent assay,to explore the relationship between the HLA-DR4 genes and the balance of TH1/TH2 in patients with RA and their clinical significance.Objective 1. To explore the association of HLA-DR4 alleles with the susceptibility and clinical features and prognosis of rheumatoid arthritis in Han nationality in Fujian; 2.. It was demonstrated that HLA-DR4 plays an important rolein development and expansion of autoimmune T cell, and triggers immune activation and disease in rheumatoid arthritis(RA). The mechanism induced the onset and development of rheumatoid arthritis remains unknown. The present study was designed to investigate the relationship between the HLA-DR4 genes and the balance of TH1/TH2 in patients with RA in an attempt to find the role of HLA-DR4 in the immune response of patients with RA.Methods: 1.The method of DNA amplification with PCR was used todertermine HLA-DR4 allels in 98 patients with RA and 100 healthy controls in Han nationality from Fujian. The duration of disease, ESR,CRP, RF, and stage based on X ray were comparatively analysed. 2. The method of DNA amplification with sequence-specific primers (PCR-SSP) was used to dertermine HLA-DR4 allels .The serum lever of INF-gamma, IL-4(the secreted pattern of TH1, TH2 cytokines) were mearsured by enzyme linked immunosorbent assay. The correlation among HLA-DR4, TH1/TH2 ratio and clinical and serum activity of disease were evaluated. The cases in study include 98 active patients with RA and 40 cases of healthy donors was envolled as controls.Results: 1.The prevalence rate of HLA-DR4 in RA was higher than that in the control group (58.1%vs 21%) .Compared with HLA-DR4 negative RA , the disease duration of positive ones was longer, the values of ESR> CRP> RF were significantly higher , joint erosive was formed in earlier stage; 2. (1): The levels of INF- gamma, IL-4 and INF-gamma /IL-4 significantly differ in RA patients and the healthy controls.(2) INF- Y /IL-4 in the HLA-DR4 positive active patients were significantly higher than that in HLA-DR4 negative active patients.Conclusio: 1. HLA-DR4 alleles are significantly associated with RA susceptibility in Han nationality in Fujian.HLA-DR4 alleles may be useful inevaluating the disease and prognosis of RA patients.2. There is an imbalance of TH cytokine production in the patients with RA , Which exhibited TH1 dominant. The ratio of INF-gamma/IL-4 is significantly different between HLA-DR4 positive RA patients and HLA-DR4 negative RA patients and significantly associated with disease activity. |
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