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HLA-DRB1 Alleles as Genetic Risk Factors for the Development of Anti-MDA5 Antibodies in Patients with Dermatomyositis.
Journal of Rheumatology 2017 September
OBJECTIVE: Patients with polymyositis/dermatomyositis (PM/DM) who express anti-melanoma differentiation associated protein 5 (anti-MDA5) antibodies frequently present with interstitial lung disease (ILD). The aim of this study was to investigate the association of HLA-DRB1 with anti-MDA5 expression in PM/DM.
METHODS: The frequency of DRB1 alleles was compared among 70 patients with PM, 104 patients with DM, and 400 healthy controls in a Han Chinese population.
RESULTS: Frequencies of DRB1*04:01 [17.0% vs 1.3%, corrected p value (pc ) = 3.8 × 10-8 , OR 16.2, 95% CI 6.6-39.7] and *12:02 (42.6% vs 19.3%, pc = 0.008, OR 3.1, 95% CI 1.7-5.7) were significantly higher in anti-MDA5-positive patients with PM/DM compared with the controls. The frequencies of DRB1*04:01 (p = 5.2 × 10-6 , OR 17.1, 95% CI 5.3-54.9) and *12:02 (p = 3.8 × 10-4 , OR 3.1, 95% CI 1.7-5.7) in anti-MDA5-positive patients with DM-ILD were higher than in the controls, whereas the frequencies of DRB1*04:01 and *12:02 did not differ between the anti-MDA5-negative patients with DM-ILD and controls. No difference in the frequency of DRB1 alleles, other than *04:01, carrying the "shared epitope" (SE), i.e., *01:01, *01:02, *04:05, and *10:01, was observed between the controls and patients with DM stratified by the presence of anti-MDA5 and ILD.
CONCLUSION: DRB1*04:01 and *12:02 confer susceptibility to anti-MDA5 antibody production in DM, which cannot be explained by the SE hypothesis.
METHODS: The frequency of DRB1 alleles was compared among 70 patients with PM, 104 patients with DM, and 400 healthy controls in a Han Chinese population.
RESULTS: Frequencies of DRB1*04:01 [17.0% vs 1.3%, corrected p value (pc ) = 3.8 × 10-8 , OR 16.2, 95% CI 6.6-39.7] and *12:02 (42.6% vs 19.3%, pc = 0.008, OR 3.1, 95% CI 1.7-5.7) were significantly higher in anti-MDA5-positive patients with PM/DM compared with the controls. The frequencies of DRB1*04:01 (p = 5.2 × 10-6 , OR 17.1, 95% CI 5.3-54.9) and *12:02 (p = 3.8 × 10-4 , OR 3.1, 95% CI 1.7-5.7) in anti-MDA5-positive patients with DM-ILD were higher than in the controls, whereas the frequencies of DRB1*04:01 and *12:02 did not differ between the anti-MDA5-negative patients with DM-ILD and controls. No difference in the frequency of DRB1 alleles, other than *04:01, carrying the "shared epitope" (SE), i.e., *01:01, *01:02, *04:05, and *10:01, was observed between the controls and patients with DM stratified by the presence of anti-MDA5 and ILD.
CONCLUSION: DRB1*04:01 and *12:02 confer susceptibility to anti-MDA5 antibody production in DM, which cannot be explained by the SE hypothesis.
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