Eun Ha Kang1, Dong Jin Go2, Tsuneyo Mimori3, Sang Jin Lee2, Hyun Mi Kwon4, Jun Won Park4, Myoung Hee Park5, Eun Young Song5, You-Jung Ha1, Eun Young Lee4, Yun Jong Lee1, Eun Bong Lee4, Yeong Wook Song6. 1. Division of Rheumatology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea. 2. Division of Rheumatology, Department of Internal Medicine, Seoul National University Hospital, 28 Yongun-dong, Chongno-gu, Seoul 110-744, South Korea; Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, College of Medicine, Seoul National University, Seoul, South Korea. 3. Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. 4. Division of Rheumatology, Department of Internal Medicine, Seoul National University Hospital, 28 Yongun-dong, Chongno-gu, Seoul 110-744, South Korea. 5. Department of Laboratory Medicine, Seoul National University Hospital, Seoul, South Korea. 6. Division of Rheumatology, Department of Internal Medicine, Seoul National University Hospital, 28 Yongun-dong, Chongno-gu, Seoul 110-744, South Korea; Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, College of Medicine, Seoul National University, Seoul, South Korea. Electronic address: ysong@snu.ac.kr.
Abstract
OBJECTIVES: HLA genes are a major genetic risk factor for myositis and myositis specific antibodies (MSAs), exhibiting unique HLA backgrounds for myositis in different ethnic groups. This is the first large scale Korean study to genotype the HLA-DRB1 and -DPB1 alleles and to examine their association with myositis and MSAs. METHODS: HLA-DRB1 and HLA-DPB1 alleles and MSAs were examined in 179 patients with dermatomyositis (DM, n = 129) or polymyositis (PM, n = 50) and healthy controls (n = 800 for HLA-DRB1, n = 548 for HLA-DPB1). Associations between individual HLA alleles and myositis/MSA were examined. Bonferroni correction was applied for multiple testing comparing patients and controls. RESULTS: A total of 33 HLA-DRB1 and 24 HLA-DPB1 alleles were genotyped in patients and controls. MSAs were found in 67.0% of patients. Anti-MDA5 (26.8%) and anti-aminoacyl-tRNA synthetase antibodies (15.6%) were most common, followed by anti-Mi2 (9.5%) and anti-TIF1γ antibodies (8.9%). HLA-DRB1*12:02 and HLA-DRB1*14:03 were associated with DM and PM, respectively. HLA-DRB1*12:02 was associated with anti-MDA5, HLA-DRB1*08:03 with anti-ARS, HLA-DRB1*14:03 with anti-SRP, and HLA-DRB1*07:01 with anti-Mi2 antibodies. Although HLA-DRB1*13:01 was associated with anti-TIF1γ antibodies, the frequency of HLA-DRB1*13:01 was rare. HLA-DPB1*02:01 was negatively associated with myositis and PM while HLA-DPB1*17:01 was associated with anti-Mi2 positive DM. CONCLUSIONS: Unique immunogenetic background was observed for Korean patients with myositis. Novel myositis susceptibility alleles, HLA-DRB1*12:02 and HLA-DRB1*14:03, were identified, together with MSA-associated HLA alleles unique to Korean patients with myositis.
OBJECTIVES:HLA genes are a major genetic risk factor for myositis and myositis specific antibodies (MSAs), exhibiting unique HLA backgrounds for myositis in different ethnic groups. This is the first large scale Korean study to genotype the HLA-DRB1 and -DPB1 alleles and to examine their association with myositis and MSAs. METHODS:HLA-DRB1 and HLA-DPB1 alleles and MSAs were examined in 179 patients with dermatomyositis (DM, n = 129) or polymyositis (PM, n = 50) and healthy controls (n = 800 for HLA-DRB1, n = 548 for HLA-DPB1). Associations between individual HLA alleles and myositis/MSA were examined. Bonferroni correction was applied for multiple testing comparing patients and controls. RESULTS: A total of 33 HLA-DRB1 and 24 HLA-DPB1 alleles were genotyped in patients and controls. MSAs were found in 67.0% of patients. Anti-MDA5 (26.8%) and anti-aminoacyl-tRNA synthetase antibodies (15.6%) were most common, followed by anti-Mi2 (9.5%) and anti-TIF1γ antibodies (8.9%). HLA-DRB1*12:02 and HLA-DRB1*14:03 were associated with DM and PM, respectively. HLA-DRB1*12:02 was associated with anti-MDA5, HLA-DRB1*08:03 with anti-ARS, HLA-DRB1*14:03 with anti-SRP, and HLA-DRB1*07:01 with anti-Mi2 antibodies. Although HLA-DRB1*13:01 was associated with anti-TIF1γ antibodies, the frequency of HLA-DRB1*13:01 was rare. HLA-DPB1*02:01 was negatively associated with myositis and PM while HLA-DPB1*17:01 was associated with anti-Mi2 positive DM. CONCLUSIONS: Unique immunogenetic background was observed for Korean patients with myositis. Novel myositis susceptibility alleles, HLA-DRB1*12:02 and HLA-DRB1*14:03, were identified, together with MSA-associated HLA alleles unique to Korean patients with myositis.
Authors: Katalin Szabó; Levente Bodoki; Melinda Nagy-Vincze; Tibor Béldi; Anett Vincze; Erika Zilahi; József Varga; Gabriella Szűcs; Katalin Dankó; Zoltán Griger Journal: Biomed Res Int Date: 2022-05-02 Impact factor: 3.246