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

Zhiyong Chen; Yan Wang; Masataka Kuwana; Xue Xu; Wei Hu; Xuebing Feng; Hong Wang; Akinori Kimura; Lingyun Sun

doi:10.3899/jrheum.170165

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

J Rheumatol. 2017 Sep;44(9):1389-1393. doi: 10.3899/jrheum.170165. Epub 2017 Jul 15.

Authors

Zhiyong Chen^{1

2}, Yan Wang^{1

2}, Masataka Kuwana^{1

2}, Xue Xu^{1

2}, Wei Hu^{1

2}, Xuebing Feng^{1

2}, Hong Wang^{1

2}, Akinori Kimura^{3

4}, Lingyun Sun^{3

4}

Affiliations

¹ From the Department of Rheumatology and Immunology, and Department of Clinical Laboratory, the Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, China; Department of Allergy and Rheumatology, Nippon Medical School Graduate School of Medicine; Department of Molecular Pathogenesis, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
² Z. Chen, MD, PhD, Department of Rheumatology and Immunology, the Affiliated Drum Tower Hospital, Nanjing University Medical School; Y. Wang, MD, Department of Rheumatology and Immunology, the Affiliated Drum Tower Hospital, Nanjing University Medical School; M. Kuwana, MD, PhD, Department of Allergy and Rheumatology, Nippon Medical School Graduate School of Medicine; X. Xu, MD, PhD, Department of Rheumatology and Immunology, the Affiliated Drum Tower Hospital, Nanjing University Medical School; W. Hu, MD, Department of Clinical Laboratory, the Affiliated Drum Tower Hospital, Nanjing University Medical School; X. Feng, MD, PhD, Department of Rheumatology and Immunology, the Affiliated Drum Tower Hospital, Nanjing University Medical School; H. Wang, MD, Department of Rheumatology and Immunology, the Affiliated Drum Tower Hospital, Nanjing University Medical School; A. Kimura, MD, PhD, Department of Molecular Pathogenesis, Medical Research Institute, Tokyo Medical and Dental University; L. Sun, MD, PhD, Department of Rheumatology and Immunology, the Affiliated Drum Tower Hospital, Nanjing University Medical School.
³ From the Department of Rheumatology and Immunology, and Department of Clinical Laboratory, the Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, China; Department of Allergy and Rheumatology, Nippon Medical School Graduate School of Medicine; Department of Molecular Pathogenesis, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan. akitis@mri.tmd.ac.jp lingyunsun2012@163.com.
⁴ Z. Chen, MD, PhD, Department of Rheumatology and Immunology, the Affiliated Drum Tower Hospital, Nanjing University Medical School; Y. Wang, MD, Department of Rheumatology and Immunology, the Affiliated Drum Tower Hospital, Nanjing University Medical School; M. Kuwana, MD, PhD, Department of Allergy and Rheumatology, Nippon Medical School Graduate School of Medicine; X. Xu, MD, PhD, Department of Rheumatology and Immunology, the Affiliated Drum Tower Hospital, Nanjing University Medical School; W. Hu, MD, Department of Clinical Laboratory, the Affiliated Drum Tower Hospital, Nanjing University Medical School; X. Feng, MD, PhD, Department of Rheumatology and Immunology, the Affiliated Drum Tower Hospital, Nanjing University Medical School; H. Wang, MD, Department of Rheumatology and Immunology, the Affiliated Drum Tower Hospital, Nanjing University Medical School; A. Kimura, MD, PhD, Department of Molecular Pathogenesis, Medical Research Institute, Tokyo Medical and Dental University; L. Sun, MD, PhD, Department of Rheumatology and Immunology, the Affiliated Drum Tower Hospital, Nanjing University Medical School. akitis@mri.tmd.ac.jp lingyunsun2012@163.com.

PMID: 28711882
DOI: 10.3899/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 (p_c) = 3.8 × 10^-8, OR 16.2, 95% CI 6.6-39.7] and *12:02 (42.6% vs 19.3%, p_c = 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.

Keywords: ANTI-MELANOMA DIFFERENTIATION-ASSOCIATED GENE 5 ANTIBODY; DERMATOMYOSITIS; HUMAN LEUKOCYTE ANTIGEN; INTERSTITIAL LUNG DISEASE; POLYMYOSITIS.

MeSH terms

Alleles
Autoantibodies / blood*
Dermatomyositis / blood
Dermatomyositis / genetics*
Dermatomyositis / immunology
Female
Gene Frequency
Genetic Predisposition to Disease*
HLA-DRB1 Chains / genetics*
Humans
Interferon-Induced Helicase, IFIH1 / immunology*
Male
Middle Aged
Risk Factors

Substances

Autoantibodies
HLA-DRB1 Chains
IFIH1 protein, human
Interferon-Induced Helicase, IFIH1