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.


METHODS
MEDLINE, bibliography review of published data, and unpublished studies.


METHODS
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.


RESULTS
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.


CONCLUSIONS
Understanding the genetic basis for autoimmune demyelination will offer new possibilities for the treatment of this illness.
Oksenberg
J R
JR
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, CA 94143-0114.
Begovich
A B
AB
Erlich
H A
HA
Steinman
L
L
D000818:Animals; D002986:Clinical Trials as Topic; D015329:Gene Rearrangement, T-Lymphocyte; D005802:Genes, MHC Class II; D005819:Genetic Markers; D006801:Humans; D007167:Immunotherapy; D009103:Multiple Sclerosis / Q000235:genetics* / Q000276:immunology / Q000628:therapy; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*
D005819:Genetic Markers; D011948:Receptors, Antigen, T-Cell