Guerreiro-Cacais Andre Ortlieb, Laaksonen Hannes, Flytzani Sevasti, N'diaye Marie, Olsson Tomas, Jagodic Maja
Neuroimmunology Unit, Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
J Inflamm Res. 2015 Nov 13;8:211-25. doi: 10.2147/JIR.S76707. eCollection 2015.
Multiple sclerosis (MS) is a complex autoimmune condition with firmly established genetic and environmental components. Genome-wide association studies (GWAS) have revealed a large number of genetic polymorphisms in the vicinity of, and within, genes that associate to disease. However, the significance of these single-nucleotide polymorphisms in disease and possible mechanisms of action remain, with a few exceptions, to be established. While the animal model for MS, experimental autoimmune encephalomyelitis (EAE), has been instrumental in understanding immunity in general and mechanisms of MS disease in particular, much of the translational information gathered from the model in terms of treatment development (glatiramer acetate and natalizumab) has been extensively summarized. In this review, we would thus like to cover the work done in EAE from a GWAS perspective, highlighting the research that has addressed the role of different GWAS genes and their pathways in EAE pathogenesis. Understanding the contribution of these pathways to disease might allow for the stratification of disease subphenotypes in patients and in turn open the possibility for new and individualized treatment approaches in the future.
多发性硬化症（MS）是一种复杂的自身免疫性疾病，具有明确的遗传和环境因素。全基因组关联研究（GWAS）已经揭示了与该疾病相关的基因附近及内部的大量遗传多态性。然而，除了少数例外情况，这些单核苷酸多态性在疾病中的意义及其可能的作用机制仍有待确定。虽然MS的动物模型——实验性自身免疫性脑脊髓炎（EAE），在总体上理解免疫以及特别是MS疾病机制方面发挥了重要作用，但从该模型中收集的关于治疗开发（醋酸格拉替雷和那他珠单抗）的许多转化信息已经得到了广泛总结。因此，在本综述中，我们希望从GWAS的角度涵盖在EAE方面所做的工作，突出那些探讨不同GWAS基因及其通路在EAE发病机制中作用的研究。了解这些通路对疾病的贡献可能有助于对患者的疾病亚表型进行分层，进而为未来新的个性化治疗方法开辟可能性。
