ERAP1 and ankylosing spondylitis.
2013
The strong
genetic associationof ERAP1 (
endoplasmic reticulum
aminopeptidase1) with
ankylosing spondylitis(AS), which is restricted to
HLA-B27positive cases, has profound pathogenetic implications. ERAP1 is involved in trimming peptides to optimal length for binding to HLA class 1 molecules, thereby not only affecting the stability and processing of
HLA-B27but also influencing the peptide repertoire presented to the immune system. This could have secondary effects on specific adaptive or autoimmune responses in AS. However, it appears increasingly likely that the pathogenic effect of ERAP1 may be mediated through effects on innate immunity, such as altering the interaction between
HLA-B27and immune receptors such as the killer immunoglobulin-like receptors (KIR) found on a range of innate immune cells or via the
endoplasmic reticulum
unfolded protein response. ERAP1 variants associated with reduced
endopeptidaseactivity appear to be protective against AS, raising the possibility that ERAP1 inhibition could represent a future treatment strategy.
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