Defining the Role of the MHC in Autoimmunity: A Review and Pooled Analysis
By M. Fernando, C. Stevens, E. Walsh, P. D. De Jager, P. Goyette, Robert M. Plenge, T. Vyse, J. Rioux. PLoS Genetics, 2008
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The major histocompatibility complex (MHC) is one of the most extensively studied regions in the human genome because of the association of variants at this locus with autoimmune, infectious, and inflammatory diseases. However, identification of causal variants within the MHC for the majority of these diseases has remained difficult due to the great variability and extensive linkage disequilibrium (LD) that exists among alleles throughout this locus, coupled with inadequate study design whereby only a limited subset of about 20 from a total of approximately 250 genes have been studied in small cohorts of predominantly European origin. We have performed a review and pooled analysis of the past 30 years of research on the role of the MHC in six genetically complex disease traits – multiple sclerosis (MS), type 1 diabetes (T1D), systemic lupus erythematosus (SLE), ulcerative colitis (UC), Crohn's disease (CD), and rheumatoid arthritis (RA) – in order to consolidate and evaluate the current literature regarding MHC genetics in these common autoimmune and inflammatory diseases. We corroborate established MHC disease associations and identify predisposing variants that previously have not been appreciated. Furthermore, we find a number of interesting commonalities and differences across diseases that implicate both general and disease-specific pathogenetic mechanisms in autoimmunity.
Subfields: Gastroenterology, Immunology, Rheumatology
View Paper: https://www.semanticscholar.org/paper/a6bb2f8173a4067ec416662cc9379a699786bd9a
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In Immunology
Citations in the corpus
- Imputing Amino Acid Polymorphisms in Human Leukocyte Antigens (2013, background): “effect sizes in autoimmune diseases, infectious diseases, severe drug reactions, and transplant medicine [2–5].”
- Present Yourself! By MHC Class I and MHC Class II Molecules (2016, background): “This likely explains why different MHC II alleles link strongly to defined auto-immune diseases [105] and immune responses against external environmental and food antigens[90].”
- Genetic heterogeneity in human disease. (2010, background): “Autoimmune conditions, such as systemic lupus erythematosis, multiple sclerosis, type I diabetes, and rheumatoid arthritis, are strongly influenced by common polymorphic variation at the histocompatibility (MHC) loci (Fernando et al., 2008).”
- Towards a systems understanding of MHC class I and MHC class II antigen presentation (2011, background): “Many MHC class II alleles are the strongest genetic markers for several autoimmune diseases, possibly owing to the peptides that they presen”