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ERAP1 in the pathogenesis of ankylosing spondylitis

Record type: Article

The endoplasmic reticulum aminopeptidase 1 (ERAP1) performs a major role in antigen processing, trimming N-terminally extended peptides to the final epitope for presentation by major histocompatibility complex class I molecules. Recent genome-wide association studies have identified single nucleotide polymorphisms (SNPs) within ERAP1 as being associated with disease, in particular ankylosing spondylitis (AS). AS is a polygenic chronic inflammatory disease with a strong genetic link to HLA-B27 known for over 40 years. The association of ERAP1 SNPs with AS susceptibility is only observed in HLA-B27-positive individuals, which intersect on the antigen processing pathway. Recent evidence examining the trimming activity of polymorphic ERAP1 highlights its role in generating peptides for loading onto and stabilizing HLA-B27, and the consequent alterations in the interaction of specific NK cell receptors, and the activation of the unfolded protein response as important in the mechanism of disease pathogenesis. Here, we discuss the recent genetic association findings linking ERAP1 SNPs with AS disease susceptibility and the effect of these variants on ERAP1 function, highlighting mechanisms by which AS may arise. The identification of these functional variants of ERAP1 may lead to better stratification of AS patients by providing a diagnostic tool and a potential therapeutic target.

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Reeves, Emma, Elliott, Tim, James, Edward and Edwards, Christopher J. (2014) ERAP1 in the pathogenesis of ankylosing spondylitis Immunologic Research, 60, (2), pp. 257-269. (doi:10.1007/s12026-014-8576-2). (PMID:25434650).

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e-pub ahead of print date: 2 December 2014
Published date: December 2014
Keywords: ERAP1, antigen processing and presentation, major histocompatibility complex, HLA-B27, ankylosing spondylitis, autoimmunity
Organisations: Cancer Sciences


Local EPrints ID: 385333
ISSN: 0257-277X
PURE UUID: c8354f17-a3a3-4b74-afb3-d165ca355399
ORCID for Tim Elliott: ORCID iD

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Date deposited: 19 Jan 2016 10:06
Last modified: 17 Jul 2017 19:57

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Author: Emma Reeves
Author: Tim Elliott ORCID iD
Author: Edward James

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