Neurology

HLA class II gene polymorphism was investigated in 100 patients with clinically definite multiple sclerosis (MS) by restriction fragment length polymorphism analysis of Taq I-digested DNA using DRB, DQA, and DQB cDNA probes.Twenty-six patients had primarily chronic progressive MS and 74 had relapsing/remitting MS. The latter group included patients with a secondary progressive evolution of symptoms. Both clinical forms of MS were found to be associated with the DRw15,DQw6 haplotpe. In addition, primarily chronic progressive MS was positively associated with theDQBl restriction fragment pattern seen in DR4,DQw8, DR7,DQw9, and DRw8, DQw4 haplotypes, as well as negatively associated with the Taq I DQBI allelic pattern corresponding to the serological specificity DQw7. Relapsing/remitting MS was positively associated with the DQBI allelic pattern observed in the DRw17,DQw2 haplotype. These three DQB1 alleles are in strong negative linkage disequilibria with DRw15. The two susceptibility markers ofeach clinical form ofMS act additively in determining the genetic susceptibility, as the relative risks for individuals carrying both markers roughly equal the sum of respective risks. Different alleles of the DQB1 locus defined by restriction fragment length polymorphisms contribute to susceptibility and resistance to primarily chronic progressive MS as well as to susceptibility to relapsing/remitting MS (4,5); i.e., the disease has a continuous progressive evolution from onset. It has been proposed that PCP MS and R/R MS may be separate disease entities (6) since they differ with respect to epidemiology (6), age at onset (4, 5, 7), initial symptoms (4, 6), prognosis with regard to degree of disability (4, 7) and to mortality (8), and response to immunosuppression (9 The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

show abstract

“…35; for review, see ref. 36). A Dw2 association has also been observed in American black MS patients.…”

Section: Discussionmentioning

confidence: 77%

“…36). In addition, the association is found to be with the RFLP pattern (T-DRB If) that corresponds to the serological DR2-split DRw15.…”

Section: Discussionmentioning

confidence: 99%

Primarily chronic progressive and relapsing/remitting multiple sclerosis: two immunogenetically distinct disease entities.

Olerup

Hillert

Fredrikson

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

220

View full text Add to dashboard Cite

show abstract

The T‐cell response to myelin basic protein in familial multiple sclerosis: Diversity of fine specificity, restricting elements, and T‐cell receptor usage

Joshi

Usuku

1993

Annals of Neurology

View full text Add to dashboard Cite

Indirect evidence suggests that an autoimmune response to myelin basic protein (MBP) may be involved in the pathogenesis of multiple sclerosis (MS). In MS, several reports have suggested that restricted T-cell populations respond to MPB, as in inbred rodents with the MS disease model experimental allergic encephalomyelitis. In experimental allergic encephalomyelitis, the T-cell repertoire to MBP varies between strains, and in MS it is likely that the response to MBP is also best defined under conditions where genetic differences between subjects are controlled. In this report, the fine specificity of the T-cell response to MBP was assessed in three families, each with multiple individuals affected with MS. We found that (1) comparable frequencies of MBP-reactive T-cell lines were obtained from peripheral blood of MS patients and their healthy siblings. Human leukocyte antigen (HLA) identical sibling pairs discordant for MS had similar frequencies of MBP-reactive T-cell lines. (2) A broad spectrum of MBP epitopes was recognized by T-cell lines from all individuals studied. Within a family, the fine specificity of MBP recognition showed little or no overlap between individuals, even between HLA identical siblings. (3) Recognition of MBP epitopes occurred in the context of different HLA class II alleles. At least four DR alleles each served as restricting elements for recognition of P82-101 or the carboxy terminal region of MBP, two regions thought to be important in the human T-cell response to the molecule. No relationship between the use of a particular DR allele and a response to a particular region of MBP could be established.(ABSTRACT TRUNCATED AT 250 WORDS)

show abstract

Genetic susceptibility to multiple sclerosis

Haegert

Marrosu

1994

Ann Neurol.

View full text Add to dashboard Cite

Twin studies have established that susceptibility to multiple sclerosis (MS) is partly genetic. Attempts to identify the relevant genetic loci have involved population-based studies, to detect associations between a genetic marker and MS, and family studies, to detect linkage between a putative marker and MS. Most of this genetic work is driven by the view that MS is an autoimmune disease. Thus, the focus has been mainly on genes known to be important in the immune response: human leukocyte antigen (HLA) genes, T-cell receptor genes, and immunoglobulin genes. To date, only the particular HLA-DR2 haplotype that is common in Caucasians can be concluded to be important in MS susceptibility in most populations. Studies of other genetic loci have been few, the data obtained often have been conflicting or controversial, and further studies are needed to clarify the biological significance of these loci in MS. Recommendations for further studies are provided in order to overcome some of the problems that have plagued earlier work in MS such as nonreproducibility of results.

show abstract

Neurology

Cited by 35 publications

References 188 publications

Primarily chronic progressive and relapsing/remitting multiple sclerosis: two immunogenetically distinct disease entities.

Primarily chronic progressive and relapsing/remitting multiple sclerosis: two immunogenetically distinct disease entities.

The T‐cell response to myelin basic protein in familial multiple sclerosis: Diversity of fine specificity, restricting elements, and T‐cell receptor usage

Genetic susceptibility to multiple sclerosis

Contact Info

Product

Resources

About