Genetic factors in multiple sclerosis
J. R. Oksenberg, A. B. Begovich, H. A. Erlich and L. Steinman
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, CA 94143-0114.
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of published data, and unpublished studies.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.
