The University of Southampton
University of Southampton Institutional Repository

Functionally distinct ERAP1 haplotype combinations define individuals with Ankylosing Spondylitis (P5047)

Functionally distinct ERAP1 haplotype combinations define individuals with Ankylosing Spondylitis (P5047)
Functionally distinct ERAP1 haplotype combinations define individuals with Ankylosing Spondylitis (P5047)
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.
0022-1767
James, E.
7dc1afb7-d326-4050-89fc-1f4e2a1a19a4
Reeves, E.
bd61ff0c-6555-47fd-884f-74dc6105e846
Colebatch, A.N.
47b9f86a-8e65-4bca-8579-5e87bbd8a571
Elliott, T.
16670fa8-c2f9-477a-91df-7c9e5b453e0e
Edwards, C.J.
dcb27fec-75ea-4575-a844-3588bcf14106
James, E.
7dc1afb7-d326-4050-89fc-1f4e2a1a19a4
Reeves, E.
bd61ff0c-6555-47fd-884f-74dc6105e846
Colebatch, A.N.
47b9f86a-8e65-4bca-8579-5e87bbd8a571
Elliott, T.
16670fa8-c2f9-477a-91df-7c9e5b453e0e
Edwards, C.J.
dcb27fec-75ea-4575-a844-3588bcf14106

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)

Record type: Article

Abstract

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.

Full text not available from this repository.

More information

Published date: 2013
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 353742
URI: http://eprints.soton.ac.uk/id/eprint/353742
ISSN: 0022-1767
PURE UUID: 732cd7f0-97c6-4fe7-a418-601610623d96
ORCID for T. Elliott: ORCID iD orcid.org/0000-0003-1097-0222

Catalogue record

Date deposited: 17 Jun 2013 09:35
Last modified: 18 Jul 2017 04:01

Export record

Contributors

Author: E. James
Author: E. Reeves
Author: A.N. Colebatch
Author: T. Elliott ORCID iD
Author: C.J. Edwards

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×