Division of Rheumatology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.
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.
Semin Arthritis Rheum. 2019 Oct;49(2):283-287. doi: 10.1016/j.semarthrit.2019.03.005. Epub 2019 Mar 9.
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.
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.
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-DRB112:02 and HLA-DRB114:03 were associated with DM and PM, respectively. HLA-DRB112:02 was associated with anti-MDA5, HLA-DRB108:03 with anti-ARS, HLA-DRB114:03 with anti-SRP, and HLA-DRB107:01 with anti-Mi2 antibodies. Although HLA-DRB113:01 was associated with anti-TIF1γ antibodies, the frequency of HLA-DRB113:01 was rare. HLA-DPB102:01 was negatively associated with myositis and PM while HLA-DPB117:01 was associated with anti-Mi2 positive DM.
Unique immunogenetic background was observed for Korean patients with myositis. Novel myositis susceptibility alleles, HLA-DRB112:02 and HLA-DRB114:03, were identified, together with MSA-associated HLA alleles unique to Korean patients with myositis.
HLA 基因是肌炎和肌炎特异性抗体（MSA）的主要遗传风险因素，在不同种族的肌炎中表现出独特的 HLA 背景。这是第一项对韩国人 HLA-DRB1 和 -DPB1 等位基因进行基因分型并研究其与肌炎和 MSA 关联的大规模研究。
在 179 名皮肌炎（DM，n=129）或多发性肌炎（PM，n=50）患者和健康对照者（HLA-DRB1 800 名，HLA-DPB1 548 名）中检查 HLA-DRB1 和 HLA-DPB1 等位基因和 MSA。检查了个体 HLA 等位基因与肌炎/MSA 之间的关联。对患者与对照组进行比较的多重检验应用了 Bonferroni 校正。
在患者和对照组中总共检测到 33 种 HLA-DRB1 和 24 种 HLA-DPB1 等位基因。67.0%的患者存在 MSA。抗 MDA5（26.8%）和抗氨酰-tRNA 合成酶抗体（15.6%）最为常见，其次是抗 Mi2（9.5%）和抗 TIF1γ 抗体（8.9%）。HLA-DRB112:02 与 DM 相关，HLA-DRB114:03 与 PM 相关。HLA-DRB112:02 与抗 MDA5 相关，HLA-DRB108:03 与抗 ARS 相关，HLA-DRB114:03 与抗 SRP 相关，HLA-DRB107:01 与抗 Mi2 抗体相关。尽管 HLA-DRB113:01 与抗 TIF1γ 抗体相关，但 HLA-DRB113:01 的频率却很少。HLA-DPB102:01 与肌炎和 PM 呈负相关，而 HLA-DPB117:01 与抗 Mi2 阳性 DM 相关。
观察到韩国肌炎患者具有独特的免疫遗传背景。确定了新的肌炎易感等位基因 HLA-DRB112:02 和 HLA-DRB114:03，以及韩国肌炎患者特有的与 MSA 相关的 HLA 等位基因。
