Zhiyong Chen1,2, Yan Wang1,2, Masataka Kuwana1,2, Xue Xu1,2, Wei Hu1,2, Xuebing Feng1,2, Hong Wang1,2, Akinori Kimura3,4, Lingyun Sun3,4. 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.
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.
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.