Department of Neurology, San Francisco School of Medicine, University of California, San Francisco, CA, USA.
Immunology. 2018 Apr;153(4):399-414. doi: 10.1111/imm.12869. Epub 2017 Dec 11.
Genes encoding antigen-presenting molecules within the human major histocompatibility complex (MHC) account for the highest component of genetic risk for many neurological diseases, such as multiple sclerosis, neuromyelitis optica, Parkinson's disease, Alzheimer's disease, schizophrenia, myasthenia gravis and amyotrophic lateral sclerosis. Myriad genetic, immunological and environmental factors may contribute to an individual's susceptibility to neurological disease. Here, we review and discuss the decades long research on the influence of genetic variation at the MHC locus and the role of immunogenetic killer cell immunoglobulin-like receptor (KIR) loci in neurological diseases, including multiple sclerosis, neuromyelitis optica, Parkinson's disease, Alzheimer's disease, schizophrenia, myasthenia gravis and amyotrophic lateral sclerosis. The findings of immunogenetic association studies are consistent with a polygenic model of inheritance in the heterogeneous and multifactorial nature of complex traits in various neurological diseases. Future investigation is highly recommended to evaluate both coding and non-coding variation in immunogenetic loci using high-throughput high-resolution next-generation sequencing technologies in diverse ethnic groups to fully appreciate their role in neurological diseases.
人类主要组织相容性复合体 (MHC) 内编码抗原呈递分子的基因是许多神经疾病（如多发性硬化症、视神经脊髓炎、帕金森病、阿尔茨海默病、精神分裂症、重症肌无力和肌萎缩侧索硬化症）的遗传风险的最高组成部分。许多遗传、免疫和环境因素可能导致个体易患神经疾病。在这里，我们回顾和讨论了几十年来关于 MHC 基因座遗传变异和免疫遗传杀伤细胞免疫球蛋白样受体 (KIR) 基因座在神经疾病（包括多发性硬化症、视神经脊髓炎、帕金森病、阿尔茨海默病、精神分裂症、重症肌无力和肌萎缩侧索硬化症）中的作用的研究。免疫遗传关联研究的结果与复杂性状的异质性和多因素性质的多基因遗传模型一致，在各种神经疾病中。强烈建议未来使用高通量高分辨率下一代测序技术在不同种族群体中评估免疫遗传基因座的编码和非编码变异，以充分了解它们在神经疾病中的作用。
