Background/Purpose: The complication of interstitial lung disease (ILD) is associated with the anti-aminoacyl tRNA synthetase antibody (ARS ab) or the anti-melanoma differentiation-associated gene 5 antibody (MDA5 ab) in polymyositis (PM)/dermatomyositis (DM). Anti-MDA5 ab is associated with clinically amyopathic DM (C-ADM) and fatal outcome due to rapidly progressive ILD (RP-ILD) in Asia. The association between genetic factors and anti-MDA5 ab-positive DM has remained unclear. We investigated the HLA-DRB1 genotype in anti-MDA5 ab-positive DM. In addition, we compared genetic differences in HLA between anti-MDA5 ab-positive DM, anti-ARS ab-positive PM/DM and PM/DM without the anti-ARS ab or ILD.

Methods: This retrospective study included patients admitted to Tokyo Women’s Medical University Aoyama Hospital or Keio University Hospital from August 1992 to February 2010. Medical records were obtained from 142 and 57 patients diagnosed as having DM and C-ADM, respectively. The anti-MDA5 antibody was detected in 31 patients. DNA samples were obtained from 17 patients with the anti-MDA5 antibody, and all of these patients were enrolled in this study. All of the enrolled patients suffered from skin rashes, myopathy, or respiratory symptoms (or a combination thereof) upon admission. These patients were diagnosed as having DM or CADM based on the criteria of Bohan and Peter or Sontheimer, respectively. To investigate the characteristics of the HLA-DRB1 genotype in anti-MDA5 ab-positive DM, we compared the genetic differences among 17 patients with anti-MDA5 ab-positive DM, 33 patients with anti-ARS ab-positive PM/DM, 33 PM/DM patients without anti-ARS ab or ILD and 265 healthy controls (HCs).

Results: The HLA-DRB1*0101 and DRB1*0405 alleles were identified in 5 (29%) patients and 12 (71%) patients, respectively, which were higher than the frequencies in HCs (10% and 25%, respectively). The HLA-DRB1*0101 or *0405 allele was identified in 16 (94%) of the 17 patients. No patients had homo alleles of HLA-DRB1*0101 or DRB1*0405. One patient had both DRB1*0101 and DRB1*0405. With respect to the clinical phenotype, 16 patients had C-ADM. ILD complication was observed in all of the patients. Moreover, the frequency of RP-ILD was high (65%). No patients had RA or other connective tissue diseases as complications.The frequency of the DRB1*0101 or 0405 allele was significantly higher in anti-MDA5 ab-positive DM patients compared with PM/DM patients without anti-ARS ab or ILD (P = 1.1e-05, odds ratio 42.7, confidence interval [CI] 4.9-370.2) or anti-ARS ab-positive PM/DM patients (P = 4.5e-03, odds ratio 13.3, CI 1.6-112.6).

Conclusion: HLA-DRB1*0101/*0405, which were defined as ‘shared epitope’ alleles in RA, is associated with susceptibility to anti-MDA5 ab positive-DM in the Japanese population. These alleles were also associated with ILD complication in PM/DM.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/hla-drb101010405-is-associated-with-susceptibility-to-anti-mda5-antibody-positive-dermatomyositis-in-the-japanese-population/