MHC Class II Risk Alleles and Amino Acid Residues in Idiopathic Membranous Nephropathy
MHC Class II Risk Alleles and Amino Acid Residues in Idiopathic Membranous Nephropathy
复制标题
特发性膜性肾病中 MHC II 类风险等位基因和氨基酸残基
DOI：
10.1681/asn.2016020114
复制
发表时间：
2017-05-01
影响因子：
13.6
通讯作者：
Zhao, Ming-hui
中科院分区：
文献类型：
--
作者：
Cui, Zhao;Xie, Li-jun;Zhao, Ming-hui
特发性膜性肾病（iMN）的靶抗原磷脂酶A2受体（PLA2R）的表位必须由HLA编码的MHC II类分子呈递，以刺激自身抗体的产生。一项全基因组关联研究发现HLA和PLA2R位点存在风险等位基因，HLA- dqa1中顶部变异rs2187668的风险效应大于PLA2R1中顶部变异rs4664308的风险效应。HLA风险等位基因如何影响iMN中MHC II类分子的表位呈递尚不清楚。在这里，我们对261名iMN患者和599名健康对照进行了HLA- drb1、HLA- dqa1、HLA- dqb1和HLA- dpb1位点的四位数分辨率基因分型，并从IMGT/HLA数据库中提取了编码的氨基酸序列。我们预测了PLA2R的T细胞表位，并利用Modeler构建了MHC-DR分子-PLA2R肽-T细胞受体结构。我们鉴定出DRB1*1501(优势比，4.65；95%可信区间[95% CI]， 3.39 ~ 6.41
Epitopes of phospholipase A2 receptor (PLA2R), the target antigen in idiopathic membranous nephropathy (iMN), must be presented by the HLA encoded MHC class II molecules to stimulate autoantibody production. A genome wide association study identified risk alleles at HLA and PLA2R loci, with the top variant rs2187668 within HLA-DQA1 showing a risk effect greater than that of the top variant rs4664308 within PLA2R1. How the HLA risk alleles affect epitope presentation by MHC class II molecules in iMN is unknown. Here, we genotyped 261 patients with iMN and 599 healthy controls at the HLA-DRB1, HLA-DQA1, HLA-DQB1, and HLA-DPB1 loci with four-digit resolution and extracted the encoded amino acid sequences from the IMGT/HLA database. We predicted T cell epitopes of PLA2R and constructed MHC-DR molecule-PLA2R peptide-T cell receptor structures using Modeler. We identified DRB1*1501 (odds ratio, 4.65; 95% confidence interval [95% CI], 3.39 to 6.41; P