Oksenberg J R, Begovich A B, Erlich H A, Steinman L
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, CA 94143-0114.
JAMA. 1993 Nov 17;270(19):2362-9.
To evaluate the role of candidate genes in the susceptibility to multiple sclerosis (MS) and describe the role of T-cell receptor (TCR) gene rearrangements in the MS brain lesion in identifying a major target of the immune response in this disease.
MEDLINE, bibliography review of published data, and unpublished studies.
Published studies using novel molecular approaches to analyze the role of the major histocompatibility complex (MHC) and TCR gene complexes, as well as other candidate genes, in susceptibility to MS. We analyze epigenetic events involving TCR genes in individuals with MS and describe recent clinical trials in which immunotherapy has been attempted.
Consistent with a polygenic model for disease predisposition, MHC and TCR gene associations with MS are relatively weak. Despite intensive research, no other putative "MS genes" have been firmly established. The analysis of TCR rearrangements in the brain lesion has helped to identify a major target of the immune response in MS.
Understanding the genetic basis for autoimmune demyelination will offer new possibilities for the treatment of this illness.
评估候选基因在多发性硬化症（MS）易感性中的作用，并描述T细胞受体（TCR）基因重排在MS脑病变中在确定该疾病免疫反应主要靶点方面的作用。
MEDLINE、已发表数据的文献综述以及未发表的研究。
使用新型分子方法分析主要组织相容性复合体（MHC）和TCR基因复合体以及其他候选基因在MS易感性中作用的已发表研究。我们分析了MS患者中涉及TCR基因的表观遗传事件，并描述了近期尝试免疫治疗的临床试验。
与疾病易感性的多基因模型一致，MHC和TCR基因与MS的关联相对较弱。尽管进行了深入研究，但尚未牢固确立其他假定的“MS基因”。对脑病变中TCR重排的分析有助于确定MS免疫反应的主要靶点。
了解自身免疫性脱髓鞘的遗传基础将为该疾病的治疗提供新的可能性。
