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Nature Research, Nature Genetics, 8(43), p. 761-767

DOI: 10.1038/ng.873

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Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility

Journal article published in 2011 by Evans Dm, Chris C. A. Spencer, Jennifer Jj Pointon, Zhan Su, Stone Ma, Udo Opperman, Udo Oppermann, David M. Evans, Matti Pirinen, Loukas Moutsianis, Millicent A. Stone, Kenna Tj, David Harvey, Ward Mm, Tom Wordsworth and other authors.
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

Ankylosing spondylitis is a common form of inflammatory arthritis predominantly affecting the spine and pelvis that occurs in approximately 5 out of 1,000 adults of European descent. Here we report the identification of three variants in the RUNX3, LTBR-TNFRSF1A and IL12B regions convincingly associated with ankylosing spondylitis (P < 5 × 10(-8) in the combined discovery and replication datasets) and a further four loci at PTGER4, TBKBP1, ANTXR2 and CARD9 that show strong association across all our datasets (P < 5 × 10(-6) overall, with support in each of the three datasets studied). We also show that polymorphisms of ERAP1, which encodes an endoplasmic reticulum aminopeptidase involved in peptide trimming before HLA class I presentation, only affect ankylosing spondylitis risk in HLA-B27-positive individuals. These findings provide strong evidence that HLA-B27 operates in ankylosing spondylitis through a mechanism involving aberrant processing of antigenic peptides.