Olsson Tomas, Jagodic Maja, Piehl Fredrik, Wallström Erik
Neuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine (L8:04), Karolinska University Hospital, 171 76 Stockholm, Sweden.
Curr Opin Immunol. 2006 Dec;18(6):643-9. doi: 10.1016/j.coi.2006.08.001. Epub 2006 Sep 14.
Detection of gene variants affecting the risk for multiple sclerosis provides insights into mechanisms central for autoaggressive neuroinflammation. Major histocompatibility complex (MHC) class II genes, and probably also MHC class I genes, regulate both human multiple sclerosis and rodent experimental autoimmune encephalomyelitis. However, the functional understanding of the MHC regulation requires further experimentation. Genome scans in human multiple sclerosis have failed to demonstrate significant non-MHC loci with genome-wide significance, but approximately 50 such loci have been described in different rodent experimental autoimmune encephalomyelitis models. Positional cloning of individual rodent genes is difficult, but genes or small genome regions now emerge. Association studies in large human cohorts are needed to confirm the human relevance of rodent genes and such cohorts will also be used for single nucleotide polymorphism-based whole-genome screening. It is realistic to assume that several non-MHC genes regulating autoimmune neuroinflammation, including target tissue responses, will be pinpointed in the next ten years. At the moment there are a few hot candidates, including MHC2TA, PRKCA and IL7R.
对影响多发性硬化症风险的基因变异进行检测，有助于深入了解自身攻击性神经炎症的核心机制。主要组织相容性复合体（MHC）II类基因，可能还有MHC I类基因，对人类多发性硬化症和啮齿动物实验性自身免疫性脑脊髓炎均有调节作用。然而，对MHC调节功能的理解还需要进一步的实验。在人类多发性硬化症的全基因组扫描中，未能发现具有全基因组意义的非MHC显著位点，但在不同的啮齿动物实验性自身免疫性脑脊髓炎模型中已描述了约50个此类位点。对单个啮齿动物基因进行定位克隆很困难，但现在已有基因或小基因组区域出现。需要在大型人类队列中进行关联研究，以确认啮齿动物基因与人类的相关性，这些队列也将用于基于单核苷酸多态性的全基因组筛查。可以合理推测，在未来十年内，将确定几个调节自身免疫性神经炎症的非MHC基因，包括靶组织反应。目前有几个热门候选基因，包括MHC2TA、PRKCA和IL7R。
