Functionally distinct ERAP1 haplotype combinations define individuals with Ankylosing Spondylitis (P5047)
James, E., Reeves, E., Colebatch, A.N., Elliott, T. and Edwards, C.J. (2013) Functionally distinct ERAP1 haplotype combinations define individuals with Ankylosing Spondylitis (P5047) Journal of Immunology, 190, (111.6)
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Ankylosing Spondylitis (AS) is a chronic inflammatory disease which commonly affects the spine occurring in approximately 0.5% of adults of European descent. In addition to HLA-B27, recent genetic linkage studies have identified polymorphisms within the aminopeptidase, ERAP1, associated with the disease. ERAP1 lies on the antigen processing pathway, generating peptide antigens for immune presentation by HLA. Here we show that ERAP1 from individuals are polymorphic and comprise haplotypes that are predominantly made up of multiple SNPs. ERAP1 haplotype combinations found in AS cases are distinct from those in controls. AS case ERAP1 haplotype combinations are unable to trim peptide precursors to generate the final epitope for presentation to T cells and are also unable to reconstitute MHC class I to normal levels as observed with control haplotype combinations. We therefore provide strong evidence that ERAP1 variation predisposes to chronic inflammatory disease via its influence on the antigen processing pathway.
|Subjects:||Q Science > QH Natural history > QH426 Genetics
Q Science > QR Microbiology > QR180 Immunology
R Medicine > RB Pathology
|Date Deposited:||17 Jun 2013 09:35|
|Last Modified:||21 Feb 2017 08:43|
|Further Information:||Google Scholar|
|RDF:||RDF+N-Triples, RDF+N3, RDF+XML, Browse.|
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