GENETIC-FACTORS IN MULTIPLE-SCLEROSIS

Objective.-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. Data Sources.-MEDLINE, bibliography review of published data, and unpublished studies. Study Selection.-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. Data Synthesis.-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. Conclusion.-Understanding the genetic basis for autoimmune demyelination will offer new possibilities for the treatment of this illness.