Endoplasmic reticulum aminopeptidase 1 and interleukin-23 receptor in ankylosing spondylitis

Abstract

Endoplasmic reticulum aminopeptidase 1 (ERAP1) and interleukin-23 receptor (IL-23R) gene polymorphisms were found to be associated with ankylosing spondylitis (AS) in a nonsynonymous single nucleotide polymorphism association study, and this has been replicated in several studies across different populations. ERAP1 variants could lead to significant changes in the repertoire of peptides presented by MHC-I. Reading this in conjunction with the known association of AS with HLA-B27, a functional interaction between ERAP1 and HLA-B27 is very likely. ERAP1 has additionally been shown to be involved in cytokine receptor shedding. The IL-23R is one of the two receptors that mediate the action of IL-23. AS is associated with the same polymorphisms of IL-23R as those linked to psoriasis and inflammatory bowel disease. This suggests common genetic risks linking AS and extra-articular manifestations. This review focuses on the pathogenic potential of these two genes in AS.