HL-A Antigen Frequencies in Multiple Sclerosis

Bertrams, J.; Kuwert, E.

doi:10.1159/000114414

Cited by 77 publications

(17 citation statements)

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“…The major histocompatibility complex (MHC) region on chromosome 6p21.32 is the first identified MS risk locus from the candidate-gene era [originally detected over 40 years ago (4, 5)] that is still valid today. As a matter of fact, with the class II HLA-DRB1*1501 allele conferring a ~3-fold risk increase [as measured by the odds ratio (OR)], the MHC region still represents the most important MS risk locus by far (6).…”

Section: Recent Advances In Ms Genetics Researchmentioning

confidence: 99%

Recent Advances and Future Challenges in the Genetics of Multiple Sclerosis

Lill

2014

Front. Neurol.

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Multiple sclerosis (MS) is the most common auto-inflammatory disease of the central nervous system, affecting more than 2 million individuals worldwide. It is a genetically complex disease, in which a substantial part of a person’s liability to develop MS is caused by a combination of multiple genetic and non-genetic (e.g., environmental) risk factors. Increasing this complexity, many of the involved risk factors likely interact in an intricate and hitherto ill-defined fashion. Despite these complexities, and owing greatly to the advent and application of large-scale genome-wide association studies, our understanding of the genetic factors underlying MS etiology has begun to gain unprecedented momentum. In this perspective, I will summarize some recent advances and outline future challenges in MS genetics research.

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Section: Recent Advances In Ms Genetics Researchmentioning

confidence: 99%

Recent Advances and Future Challenges in the Genetics of Multiple Sclerosis

Lill

2014

Front. Neurol.

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“…HLA Genes First reports that HLA-A3 and -B7 are associated with MS in Northern American and Northern European MS populations date back to the early 1970s (99). Analogous to other autoimmune diseases and EAE, stronger associations have, however, been observed with HLA-class II genes, namely HLA-DR2 1 (100).…”

Section: Genetic Factorsmentioning

confidence: 99%

“…TCL were established, and the fi ne specifi city was assessed by both proliferation and cytotoxicity (130,131). Two peptides located in the middle of the molecule (87)(88)(89)(90)(91)(92)(93)(94)(95)(96)(97)(98)(99)(100)(101)(102)(103)(104)(105)(106) and at the C-terminus (154-172) which had been used previously (128) were recognized by a large fraction of TCL from both groups (131). In a second investigation, MBP specific cytotoxic TCL were established from comparable percentages of MS patients and controls (13 1).…”

Section: Fine Specificity Of Mbp-specific T Cellsmentioning

confidence: 99%

Immunological Aspects of Demyelinating Diseases

Martin

McFarland

McFarlin

1992

Annu. Rev. Immunol.

942

221

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Primary demyelination in the central nervous system results from damage to the myelin sheath or oligodendroglia and can be produced by a variety of mechanisms, including metabolic disturbances, toxicities, infection, and autoimmunity. The major human demyelinating disease affecting the central nervous system is multiple sclerosis (MS). Although the etiology of MS is not known, existing data indicate that both genetic and environmental factors contribute to pathogenesis. Experimental allergic encephalomyelitis (EAE) is induced by immunization of genetically susceptible animals with myelin proteins. This is mediated by autoimmune T cells. Characterization of MHC restriction, fine specificity of antigen recognition, and T cell receptor (TCR) usage by encephalitogenic T cells has resulted in highly specific immunotherapies. Both HLA and TCR genes have been linked to susceptibility for MS which is widely believed to be mediated by T cells that recognize an as yet unidentified autoantigen. Because of the advances in the understanding and treatment of EAE, recent research in MS has been focused on the characterization of cellular immune responses against myelin components. The results of these studies are reviewed and the potential implications of these findings for the pathogenesis and future therapy of MS are examined.

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“…of HLA-A3, -B7, or -DR2 allele(s) (2)(3)(4), with the strongest association involving HLA-DR2 (5), as recently reviewed (1,6,7). In contrast to this well established HLA-related susceptibility, the importance of HLA-B7 or -DR2 in MS severity remains controversial (5,7,8).…”

Section: Introductionmentioning

confidence: 99%

Combined influences of Gm and HLA phenotypes upon multiple sclerosis susceptibility and severity.

Salier¹,

Sesboüé²,

Martin-Mondiere³

et al. 1986

J. Clin. Invest.

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In some Caucasian populations, multiple sclerosis (MS) susceptibility has been independently related to given alleles of HLA or Gm systems that respectively code for majorhistocompatibility complex class I and II antigens or immunoglobulin G heavy chains. Whether given combinations of alleles at both series of loci simultaneously influence MS susceptibility and/or severity was investigated by comparing 147 French MS patients and 226geographically-matched healthy controls. The G2m(-23)/HLA-B35 phenotype and Glm(-1)/HLA-B7(-)/HLA-DR2 phenotype were respectively associated with significant protection against (relative risk = 0.05) and susceptibility to (relative risk = 43) MS. When considering MS severity, the presence of HLA-B7 antigen correlated with a more severe disease in Gmn/Gm3 heterozygous patients, but not in Gm33/Gm3 homozygous patients.Conversely, an HLA-B12-associated milder disease was restricted to Gm3/Gm3 homozygotes. These results demonstrate the combined influence on MS of genetic loci that are unlinked but immune response-associated. Combined Gm and HLA typing is very likely able to serve as a prognostic indicator in this disease.

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HL-A Antigen Frequencies in Multiple Sclerosis

Cited by 77 publications

References 0 publications

Recent Advances and Future Challenges in the Genetics of Multiple Sclerosis

Recent Advances and Future Challenges in the Genetics of Multiple Sclerosis

Immunological Aspects of Demyelinating Diseases

Combined influences of Gm and HLA phenotypes upon multiple sclerosis susceptibility and severity.

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