The human leukocytes antigen (HLA)-DRB1*16:02 allele has been suggested to be associated with many autoimmune diseases. However, a validation of the results of the different studies by a comprehensive analysis of the corresponding meta data is lacking. In this study, we performed a meta-analysis of the association between HLA-DRB1*16:02 allele with various autoimmune disorders. Our analysis shows that HLA-DRB1*16:02 allele was associated with systemic lupus erythematosus, anti-N-Methyl-d-Aspartate receptor (NMDAR) encephalitis, Graves' disease, myasthenia gravis, neuromyelitis optica and antibody-associated systemic vasculitis with microscopic polyangiitis (AASV-MPA). However, no such association was found for multiple sclerosis, autoimmune hepatitis type 1, rheumatoid arthritis, type 1 diabetes and Vogt-Koyanagi-Harada syndrome. Re-analysis of the studies after their categorization into autoantibody-dependent and T cell-dependent autoimmune diseases revealed that the HLA-DRB1*16:02 allele was strongly associated with disorder predominantly mediated by autoantibodies (OR = 1.93; 95% CI = 1.63-2.28, P = 1.95 × 10-14) but not with those predominantly mediated by T cells (OR = 1.08; 95% CI = 0.87-1.34, P = .474). In addition, amino acid sequence alignment of common HLA-DRB1 subtypes demonstrated that HLA-DRB1*16:02 carries a unique motif of amino acid residues at position 67-74 which encodes the third hypervariable region. Taken together, the distinct pattern of disease association and the unique amino acid sequence of the third hypervariable region of the HLA-DRB1 provide some hints on how HLA-DRB1*16:02 is involved in the pathogenesis of autoimmune diseases.

中文翻译：

---

全面的荟萃分析显示，HLA-DRB1 * 1602等位基因与主要由自身抗体介导的自身免疫性疾病有关。

已建议人类白细胞抗原（HLA）-DRB1 * 16：02等位基因与许多自身免疫性疾病相关。但是，缺乏通过对相应的元数据进行综合分析来验证不同研究结果的方法。在这项研究中，我们对HLA-DRB1 * 16：02等位基因与各种自身免疫性疾病之间的关联进行了荟萃分析。我们的分析显示，HLA-DRB1 * 16：02等位基因与系统性红斑狼疮，抗N-甲基-d-天冬氨酸受体（NMDAR）脑炎，格雷夫斯病，重症肌无力，视神经脊髓炎和抗体相关的系统性血管炎相关显微镜下多血管炎（AASV-MPA）。但是，未发现多发性硬化症，1型自身免疫性肝炎，类风湿性关节炎，1型糖尿病和Vogt-Koyanagi-Harada综合征的相关性。将研究分类为自身抗体依赖性和T细胞依赖性自身免疫疾病后，对研究进行了重新分析，结果显示HLA-DRB1 * 16：02等位基因与主要由自身抗体介导的疾病密切相关（OR = 1.93； 95％CI = 1.63 -2.28，P = 1.95×10-14），而不是主要由T细胞介导的那些（OR = 1.08； 95％CI = 0.87-1.34，P = .474）。此外，常见的HLA-DRB1亚型的氨基酸序列比对证明HLA-DRB1 * 16：02在编码第三个高变区的67-74位带有一个独特的氨基酸残基基序。总之，疾病关联的独特模式和HLA-DRB1第三高变区的独特氨基酸序列为HLA-DRB1 * 16：02如何参与自身免疫性疾病的发病机理提供了一些提示。