Rheumatoid Arthritis Research Today is a free monthly online journal that collates and summarizes the latest research about Rheumatoid Arthritis, including details on treatment, symptoms, causes, medication. | ||||||||
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HLA-DMA*0103 and HLA-DMB*0104 alleles as novel prognostic factors in rheumatoid arthritis.Morel J, Roch-Bras F, Molinari N, Sany J, Eliaou JF, Combe B Department of Immuno-Rheumatology, Hospital Lapeyronie 34295, Montpellier cedex 5, France. j-morel@chu-montpellier.fr. OBJECTIVE: To evaluate HLA-DM alleles as markers for disease severity in rheumatoid arthritis (RA). METHODS: Two distinct cohorts of patients with RA were oligotyped for HLA-DB1 and HLA-DM genes using PCR amplified genomic DNA with sequence specific oligonucleotide probes. Cohort 1 comprised 199 unselected patients with RA (mean (SD) age 45.5 (13.5) years; disease duration 11.9(8.8) years), whose disease severity was assessed using Larsen score on hand and foot radiographs. Cohort 2 comprised 95 patients with severe RA and 70 patients with benign RA according to the Larsen method. RESULTS: In cohort 1, after stratification according to DRB1 genotypes, patients positive for HLA-DMA*0103 and negative for HLA-DRB1*04 tended to have greater articular damage on hands and wrists (p = 0.07 by Mann-Whitney U test) and reached statistical significance for the Larsen score per year (p = 0.05). This association between HLA-DMA*0103 and articular damage was especially observed in patients with HLA-DRB1*01. Similarly, HLA-DMB*0104 positive patients had higher Larsen score on hands and wrists (p = 0.02). This association was even stronger in DRB1*04 positive patients (p = 0.005). In cohort 2, HLA-DMA*0103 was associated with severe RA in patients negative for HLA-DRB1*04 (OD = 5.4; p = 0.014). HLA-DMB*0104 allele frequency tended to be higher in patients with severe RA but without reaching significance. CONCLUSION: This is the first study evaluating the role of HLA-DM genes in the severity of RA. Our results suggest that HLA-DMA*0103 and HLA-DMB*0104 alleles may represent new genetic markers of RA severity. The HLA-DMA*0103 allele tends to be associated with patients with RA negative for DRB1*04 and could predict a more severe form of disease especially in HLA-DRB1*01 positive patients. The HLA-DMB*0104 allele could have an additive effect in HLA-DRB1*04 patients. Combined determination of HLA-DM and HLA-DRB1 alleles could facilitate identification of patients likely to have a poor disease course. Published 19 November 2004 in Ann Rheum Dis, 63(12): 1581-6.
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