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HLA-DRB1 Alleles as Genetic Risk Factors for the Development of Anti-MDA5 Antibodies in Patients with Dermatomyositis.

HLA-DRB1 Alleles as Genetic Risk Factors for the Development of Anti-MDA5 Antibodies in Patients with Dermatomyositis.
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Chen Z, Wang Y, Kuwana M, Xu X, Hu W, Feng X, Wang H, Kimura A, Sun L,


Chen Z, Wang Y, Kuwana M, Xu X, Hu W, Feng X, Wang H, Kimura A, Sun L, (click to view)

Chen Z, Wang Y, Kuwana M, Xu X, Hu W, Feng X, Wang H, Kimura A, Sun L,

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The Journal of rheumatology 2017 07 15() pii jrheum.170165
Abstract
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.

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