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November 17, 1993, Vol 270, No. 19 >
ARTICLE | November 17, 1993

Genetic Factors in Multiple Sclerosis FREE

Jorge R. Oksenberg, PhD; Ann B. Begovich, PhD; Henry A. Erlich, PhD; Lawrence Steinman, MD
[+] Author Affiliations

Reprint requests to Department of Neurology, M-794, School of Medicine, University of California, San Francisco, 505 Parnassus Ave, San Francisco, CA 94143-0114 (Dr Oksenberg).


JAMA. 1993;270(19):2362-2369. doi:10.1001/jama.1993.03510190118037
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References

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  —MEDLINE, bibliography review of published data, and unpublished studies.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.(JAMA. 1993;270:2362-2369)

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Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

1 +
Ebers GC, Bulman DE, Sadovnick AD, et al.  A population-based study of multiple sclerosis in twins. N Engl J Med . 1986;;315:1638-1642.
2 +
Kurtzke JF.  Epidemiology of MS.  In: Hallpike JF, Adams CWM, Tourtellote WW, eds. Multiple Sclerosis . Baltimore, Md: Williams & Wilkins; 1983;:49-95.
3 +
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4 +
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5 +
Campbell RD, Trowsdale J.  Map of the human MHC. Immunol Today . 1993;;14:349-352.
6 +
Unanue ER.  Cellular studies on antigen presentation by class II MHC molecules. Curr Opin Immunol . 1992;;4:63-69.
7 +
Pullen AM, Kappler JW, Marrack P.  Tolerance to self antigens shapes the T-cell repertoire. Immunol Rev . 1989;;107:125-139.
8 +
Todd JA, Acha-Orbea H, Bell JI, et al.  A molecular basis for MHC class II-associated autoimmunity. Science . 1988;;240:1003-1009.
9 +
Nepom G, Erlich HA.  MHC-class II molecules and autoimmunity. Annu Rev Immunol . 1991;;9: 493-525.
10 +
Bertrams J, Kuwert E, Liedtke U.  HLA antigens and multiple sclerosis. Tissue Antigens . 1972;; 2:405-408.
11 +
Maito S, Manerow N, Mickey MR, Terasaki PI.  Multiple sclerosis: association with HL-A3. Tissue Antigens . 1972;;2:1-4.
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Jersild C, Fog T, Hansen GS, et al.  Histocompatibility determinants in multiple sclerosis. Lancet . 1973;;2:1221-1225.
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Oksenberg JR, Steinman L.  The role of the MHC and T cell receptor in susceptibility to multiple sclerosis. Curr Opin Immunol . 1990;;2:619-621.
14 +
Olerup O, Hillert J, Fredrikson S, et al.  Primarily chronic progressive and relapsing/remitting MS: two immunogenetically distinct disease entities. Proc Natl Acad Sci U S A . 1989;;86:7113-7117.
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Vartdal F, Sollid L, Vandvik B, Markussen G, Thorsby E.  Patients with multiple sclerosis carry DQβ1 genes which encode shared polymorphic amino acid sequences. Hum Immunol . 1989;;25:103-110.
16 +
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