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HLA DR 4 alleles in Rheumatoid arthritis Patients: Relation to severity and response to methotrexate therapy

1Farha A. El-Chennawy, 1Shirin S. Metwally, 2Waheed A. Sultan

1Immunology Unit, Clinical Pathology Department, 2Rheumatology and Rehabilitation Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt.

The aim of this study is to analyse HLA-DR 4 alleles in Egyptian patients with rheumatoid arthritis (RA) and to evaluate the effect of the responsible allele on the severity of the disease and on the response to methotrexate (MTX) therapy. The study group comprised 20 patients with RA (15 females and 5 males) with age ranged between 31 50 years. Ten healthy subjects were considered as controls. For HLA DRB1 typing, 121 healthy subjects, were considered as controls. HLA DRB1 typing were performed using reverse dot blot hybridization after amplification of the extracted DNA using PCR, other parameters include CBC, ESR, CRP and Rheumatoid factor (RF) estimation. Our results revealed that DRB1* 0402 allele is the most frequent allele in patients with RA (40%) compared to controls (5.8 %), followed by DRB1* 0403 which is found in (20%) of our patients compared to controls (4.1%), DRB1* 1101 allele was found to be very frequent in normal Egyptian controls (32.2%) while in RA patients it was 10% only. The frequency of erosion and deformity in DR4 positive patients were 91.7% and 66.7%, respectively, compared to DR4 negative patients, 37.5% and 12.5%, respectively. Significantly increased frequency of erosion and deformity in patients with *0402 allele (100%) compared to patients lacking it (26.6%,) and significant association between the presence of *0402 allele and the unresponsiveness to MTX therapy were observed. We conclude that DRB1 *0402 and *0403 are the most frequent alleles in Egyptian RA patients, there is a significant association between *0402 positive patients and disease severity in the form of erosion and deformity. Lastly the presence of DRB1 *0402 allele may be associated with resistance to MTX therapy.