Modern technological innovations have advanced our understanding of the genetic basis of spondyloarthritis. In ankylosing spondylitis (AS), where the major histocompatibility complex (MHC) accounts for nearly half of the predisposition, most comes from HLA-B27, for which 65 subtypes are now recognised, although other genes are also at work including HLA-B60 (B*40:01). Other genes have been identified, including those involved in peptide editing for loading onto class I MHC molecules (ERAP1) and cytokine genes such as interleukin 1A (IL-1A) and those involved in the Th17 network (IL-23R, an association seen primarily in Caucasians) and others. In acute anterior uveitis, these associations are also seen as well as a region on chromosome 9p and genes whose confirmation is under way. Psoriasis and psoriatic arthritis fall into this disease spectrum, with the largest region of susceptibility coming from the MHC (most likely HLA-C, ie, C*06:02 although additional influences are also being implicated), and most of the other genetic susceptibility coming from genes involved in cytokine production, specifically genes in the Th17 pathway (IL-12B, IL-23A and IL-23R, the latter, like in AS, not seen in Asians), genes in the nuclear factor κB pathway (TNFAIP3 and TNIP1) and genes in the Th2 pathway (IL-4 and IL-13). Given that more than half of patients with AS have evidence on colonoscopy of at least occult inflammatory bowel disease (IBD), it is not surprising that shared genetic influences are operative. In IBD, genes important in the innate immune response (NOD2), autophagy (ATG6L1) and regulation of the IL-23 pathway (IL-23R) play a role in disease susceptibility.
Statistics from Altmetric.com
Funding This study was supported by grant P01-052915-01.
Competing interests None.
Provenance and peer review Not commissioned; externally peer reviewed.
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.