HL‐A Antigens and Multiple Sclerosis

Bertrams, J.; Kuwert, E.; Liedtke, U

doi:10.1111/j.1399-0039.1972.tb00060.x

Cited by 109 publications

(16 citation statements)

References 7 publications

(7 reference statements)

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“…The HLA (Box 1) association with MS, which was first described several decades ago [25, 26], is consistent with the idea that MS is, at its core, an antigen-specific autoimmune disease. The association of the HLA locus with MS risk has been observed across all populations studied, and in both primary progressive and relapsing-remitting patients.…”

Section: The Human Leukocyte Antigen [Hla] Region and Mssupporting

confidence: 78%

“…The influence of HLA in MS susceptibility was first recognized prior to the molecular description of the class II molecules, and based on association with the serological specificity LD-7a determinant [25, 30–32], which was initially linked to HLA-A3 and - B7; with the latter giving the strongest association signal. Subsequently, it was demonstrated that these class I alleles were part of an extended class I and class II haplotype, and that the serological determinant was likely recognizing Dw2 , whose serological specificity is now known as DR2 [33–35].…”

Section: The Human Leukocyte Antigen [Hla] Region and Msmentioning

confidence: 99%

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The immunogenetics of multiple sclerosis: A comprehensive review

Hollenbach

Oksenberg

2015

Journal of Autoimmunity

314

218

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Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system and common cause of non-traumatic neurological disability in young adults. The likelihood for an individual to develop MS is strongly influenced by her or his ethnic background and family history of disease, suggesting that genetic susceptibility is a key determinant of risk. Over 100 loci have been firmly associated with susceptibility, whereas the main signal genome-wide maps to the class II region of the human leukocyte antigen (HLA) gene cluster and explains up to 10.5% of the genetic variance underlying risk. HLA-DRB1*15:01 has the strongest effect with an average odds ratio of 3.08. However, complex allelic hierarchical lineages, cis/trans haplotypic effects, and independent protective signals in the class I region of the locus have been described as well. Despite the remarkable molecular dissection of the HLA region in MS, further studies are needed to generate unifying models to account for the role of the MHC in disease pathogenesis. Driven by the discovery of combinatorial associations of Killer-cell Immunoglobulin-like Receptor (KIR) and HLA alleles with infectious, autoimmune diseases, transplantation outcome and pregnancy, multi-locus immunogenomic research is now thriving. Central to immunity and critically important for human health, KIR molecules and their HLA ligands are encoded by complex genetic systems with extraordinarily high levels of sequence and structural variation and complex expression patterns. However, studies to-date of KIR in MS have been few and limited to very low resolution genotyping. Application of modern sequencing methodologies coupled with state of the art bioinformatics and analytical approaches will permit us to fully appreciate the impact of HLA and KIR variation in MS.

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Section: The Human Leukocyte Antigen [Hla] Region and Mssupporting

confidence: 78%

Section: The Human Leukocyte Antigen [Hla] Region and Msmentioning

confidence: 99%

The immunogenetics of multiple sclerosis: A comprehensive review

Hollenbach

Oksenberg

2015

Journal of Autoimmunity

314

218

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“…The polymorphism of many of the HLA genes is extraordinary, with more than 14,000 alleles identified to date; more than 100 infectious, autoimmune and inflammatory disease phenotypes, including MS, as well as drug reactions and cancers are associated with HLA genes variation [84, 85]. The association of the HLA locus with MS risk was first described several decades ago [86] and since then has been observed across all populations studied [87]. HLA-DRB1 allelic heterogeneity vis-a-vis MS risk and copy number effects have been described [88].…”

Section: Mhc Boxmentioning

confidence: 99%

The Genetics of Multiple Sclerosis: From 0 to 200 in 50 Years

2017

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Multiple sclerosis (MS) is a common autoimmune disease that targets myelin in the central nervous system (CNS). Multiple GWAS in the last 10 years have uncovered more than 200 loci that independently contribute to disease pathogenesis. As with many other complex diseases, risk to MS is driven by multiple common variants whose biological effects are not immediately clear. This review will present a historical perspective on the progress made on MS genetics and discuss current work geared towards creating a more complete model that accurately represents the genetic landscape of MS susceptibility. Such a model necessarily includes a better understanding of the individual contributions of each common variant to the cellular phenotypes, and interactions with other genes and with the environment. Future genetic studies in MS will likely focus on the role of rare variants and endophenotypes.

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“…The first evidence for the association of HLA class I antigens with MS was published in 1972, 29 with risk for MS initially reported to be associated with HLA-A*03 and HLA-B*07 29,30 on the basis of their serological specificity. [29][30][31][32] It later became apparent that these class I alleles were part of an extended class I and class II haplotype, associated with the serological determinant Dw2, 33 later renamed DR2. 34 The advancement in HLA genotyping approaches and continuous investigation of this region in MS ultimately revealed that the DR2 specificity has two distinctive molecular allotypes, DR*15 and DR*16, and the correlation with MS was pinpointed to DRB1*15:01, 35 a subtype of DRB1*15.…”

Section: Hla and Multiple Sclerosismentioning

confidence: 99%

The immunogenetics of neurological disease

2017

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Summary Genes encoding antigen‐presenting molecules within the human major histocompatibility complex (MHC) account for the highest component of genetic risk for many neurological diseases, such as multiple sclerosis, neuromyelitis optica, Parkinson's disease, Alzheimer's disease, schizophrenia, myasthenia gravis and amyotrophic lateral sclerosis. Myriad genetic, immunological and environmental factors may contribute to an individual's susceptibility to neurological disease. Here, we review and discuss the decades long research on the influence of genetic variation at the MHC locus and the role of immunogenetic killer cell immunoglobulin‐like receptor (KIR) loci in neurological diseases, including multiple sclerosis, neuromyelitis optica, Parkinson's disease, Alzheimer's disease, schizophrenia, myasthenia gravis and amyotrophic lateral sclerosis. The findings of immunogenetic association studies are consistent with a polygenic model of inheritance in the heterogeneous and multifactorial nature of complex traits in various neurological diseases. Future investigation is highly recommended to evaluate both coding and non‐coding variation in immunogenetic loci using high‐throughput high‐resolution next‐generation sequencing technologies in diverse ethnic groups to fully appreciate their role in neurological diseases.

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HL‐A Antigens and Multiple Sclerosis

Cited by 109 publications

References 7 publications

The immunogenetics of multiple sclerosis: A comprehensive review

The immunogenetics of multiple sclerosis: A comprehensive review

The Genetics of Multiple Sclerosis: From 0 to 200 in 50 Years

The immunogenetics of neurological disease

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