The HLA region and autoimmune disease: associations and mechanisms of action

Gough, S .C. L. and Simmonds, Matthew J. (2007) The HLA region and autoimmune disease: associations and mechanisms of action. Current Genomics, 8 (7). pp. 453-465. ISSN 1389-2029

2007 Current Genomics HLA review.pdf

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The HLA region encodes several molecules that play key roles in the immune system. Strong association between the HLA region and autoinumme disease (AID) has been established for over fifty years. Association of components of the HLA class II encoded HLA-DRB1-DQA1-DQB1 haplotype has been detected with several AIDs, including rheumatoid arthritis, type 1 diabetes and Graves' disease. Molecules encoded by this region play a key role in exogenous antigen presentation to CD4+ Th cells, indicating the importance of this pathway in AID initiation and progression. Although other components of the HLA class I and III regions have also been investigated for association with AID, apart from the association of HLA-B*27 with ankylosing spondylitis, it has been difficult to determine additional susceptibility loci independent of the strong linkage disequilibrium (LD) with the HLA class II genes. Recent advances in the statistical analysis of LD and the recruitment of large AID datasets have allowed investigation of the HLA class I and III regions to be re-visited. Association of the HLA class I region, independent of known HLA class II effects, has now been detected for several AIDs, including strong association of HLA-B with type 1 diabetes and HLA-C with multiple sclerosis and Graves' disease. These results provide further evidence of a possible role for bacterial or viral infection and CD8+ T cells in AID onset. The advances being made in determining the primary associations within the HLA region and AlDs will not only increase our understanding of the mechanisms behind disease pathogenesis but may also aid in the development of novel therapeutic targets in the future. © 2007 Bentham Science Publishers Ltd.

Keywords:HLA antigen, HLA antigen class 1, HLA antigen class 2, HLA antigen class 3, HLA B antigen, HLA B27 antigen, HLA C antigen, HLA DQA1 antigen, HLA DQB1 antigen, HLA DR antigen, unclassified drug, acquired immune deficiency syndrome, Addison disease, ankylosing spondylitis, antigen presentation, autoimmune disease, bacterial infection, CD4+ T lymphocyte, CD8+ T lymphocyte, celiac disease, disease course, gene linkage disequilibrium, genetic association, genetic susceptibility, Graves disease, haplotype, Hashimoto disease, HLA system, immune system, insulin dependent diabetes mellitus, multiple sclerosis, myasthenia gravis, pathogenesis, review, rheumatoid arthritis, systemic lupus erythematosus, virus infection, Bacteria (microorganisms)
Subjects:C Biological Sciences > C420 Human Genetics
Divisions:College of Science > School of Life Sciences
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ID Code:22624
Deposited On:01 Apr 2016 08:53

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