Myelin oligodendrocyte glycoprotein-associated disorders are associated with HLA subtypes in a Chinese paediatric-onset cohort
Myelin oligodendrocyte glycoprotein-associated disorders are associated with HLA subtypes in a Chinese paediatric-onset cohort
复制标题
中国儿科发病队列中髓鞘少突胶质细胞糖蛋白相关疾病与 HLA 亚型相关
DOI：
10.1136/jnnp-2019-322115
复制
发表时间：
2020-07-01
影响因子：
11
通讯作者：
Peng, Lisheng
中科院分区：
文献类型：
--
作者：
Sun, Xiaobo;Qiu, Wei;Peng, Lisheng
目的髓鞘少突胶质细胞糖蛋白相关疾病（MOGAD）是一种罕见的新型神经系统自身免疫性疾病，发病机制尚不清楚。由于该疾病与人类白细胞抗原（HLA）的联系尚未显示，我们在这里调查MOGAD是否与HLA基因座相关。方法将2016年至2018年来自三个学术中心的95名MOGAD患者的HLA基因型与481名健康中国汉族人进行比较。MOGAD患者包括51例儿童发病和44例成人发病病例。所有患者的髓鞘少突胶质细胞糖蛋白（MOG）靶向IgG血清阳性。结果儿童MOGAD与HLA Ⅱ类基因DQB 1 *05：02-DRB 1 *16：02等位基因（OR=2.43; OR=3.28）或单倍型（OR=2.84）相关。这些基因型在儿童MOGAD患者中的患病率显著高于健康对照组（padj=0.0154; padj=0.0221; padj=0.0331）。相比之下，成人发病MOGAD与任何HLA基因型无关。在临床上，具有DQB 1 *05：02-DRB 1 *16：02单倍型的患者在发病时表现出显著更高的扩展残疾状态量表评分（p=0.004），并且更可能经历疾病复发（p=0.030）。HLA-肽结合预测算法和计算对接分析为MOG肽亚基和DQB 1 *05：02等位基因之间的密切关系提供了支持性证据。体外实验结果表明，预测的靶序列的位点特异性突变降低了抗原-抗体结合，尤其是在具有DQB 1 *05：02等位基因的儿童发病组中。结论本研究证实了特异性HLA II类等位基因与儿童发病MOGAD之间可能存在关联，为儿童和成人发病MOGAD可能存在不同病因和发病机制的推测提供了证据。
Objective Myelin oligodendrocyte glycoprotein-associated disorders (MOGADs) are a rare new neurological autoimmune disease with unclear pathogenesis. Since a linkage of the disease to the human leucocyte antigen (HLA) has not been shown, we here investigated whether MOGAD is associated with the HLA locus. Methods HLA genotypes of 95 patients with MOGADs, assessed between 2016 and 2018 from three academic centres, were compared with 481 healthy Chinese Han individuals. Patients with MOGADs included 51 paediatric-onset and 44 adult-onset cases. All patients were seropositive for IgG targeting the myelin oligodendrocyte glycoprotein (MOG). Results Paediatric-onset MOGAD was associated with the DQB1*05:02–DRB1*16:02 alleles (OR=2.43; OR=3.28) or haplotype (OR=2.84) of HLA class II genes. The prevalence of these genotypes in patients with paediatric-onset MOGAD was significantly higher than healthy controls (padj=0.0154; padj=0.0221; padj=0.0331). By contrast, adult-onset MOGAD was not associated with any HLA genotype. Clinically, patients with the DQB1*05:02–DRB1*16:02 haplotype exhibited significantly higher expanded disability status scale scores at onset (p=0.004) and were more likely to undergo a disease relapse (p=0.030). HLA–peptide binding prediction algorithms and computational docking analysis provided supporting evidence for the close relationship between the MOG peptide subunit and DQB1*05:02 allele. In vitro results indicated that site-specific mutations of the predicted target sequence reduced the antigen–antibody binding, especially in the paediatric-onset group with DQB1*05:02 allele. Conclusions This study demonstrates a possible association between specific HLA class II alleles and paediatric-onset MOGAD, providing evidence for the conjecture that different aetiology and pathogenesis likely underlie paediatric-onset and adult-onset cases of MOGAD.