The spondyloarthropathies (SpA) now better termed spondyloarthritides (SpAs) are a group of diverse interrelated inflammatory arthritides which share multiple clinical features as well as common genetic predisposing factors. The group includes the prototypical disease ankylosing spondylitis (AS), reactive arthritis (ReA) or spondyloarthritis, psoriatic arthritis (PsA) or spondyloarthritis, SpA associated with inflammatory bowel disease (IBD) (Crohn's disease or ulcerative colitis), undifferentiated SpA (uSpA) and juvenile-onset spondyloarthritis. (From Ehrenfeld 2012 and references therein, pubmed:22424199.)

Spondyloarthritides are characterised by sacroiliitis with inflammatory back pain, peripheral arthropathy (joint disease), absence of rheumatoid factor and subcutaneous nodules, enthesitis (inflammation of entheses, sites where tendons or ligaments insert into bone), and extra-articular or extra-spinal involvement, including of the eye, heart, lung and skin. (Adapted from Taurog et al. 2016, pubmed:27355535.)

Spondyloarthropathy (SpA), one of the commonest chronic rheumatic diseases, includes a spectrum of related disorders comprising the prototype ankylosing spondylitis (AS), a subset of psoriatic arthritis (PsA), reactive arthritis (ReA), arthritis associated with inflammatory bowel disease, and undifferentiated spondyloarthropathy (Miceli-Richard et al. 2004, pubmed:15234954). [from MIM:106300, 2020.02.25]

A strong genetic predisposition was confirmed by the discovery of a remarkably high association between AS and the human leukocyte antigen (HLA)-B27 in 1973. A proportion of AS cases that do not involve HLA-B27 have been reported, however, it is still regarded as one of the most important factors for the development of AS with a high association (>100), and is present in up to 90% of patients in the majority of ethnic groups that present with the disease. Genetic studies have concluded that HLA-B27 in the major histocompatibility complex (MHC) locus contributes to ~20.1% of AS heritability, with 4.3% associated with loci other than HLA-B. It has a high degree of genetic polymorphism, with up to 105 known subtypes, termed HLA-B* 27:01 to HLA-B* 27:106 , which are encoded by 132 alleles. The most common subtypes associated with AS are HLA-B* 27:05 (Caucasians), HLA-B* 27:04 (Chinese), and HLA-B* 27:02 (Mediterranean). However, two subtypes, HLA-B* 27:06 and HLA-B* 27:09 , do not appear to present any association with the disease. In addition, genome-wide association studies and those involving Immunochip arrays, have further substantiated that the development of AS is determined, to a large extent, by genes located outside of the MHC locus. These involve loci of the interleukin (IL)-23/IL-17 axis, including IL23R, IL12B, tyrosine kinase 2, signal transducer and activator of transcription 3, IL6R, IL27, as well as several aminopeptidase genes, including endoplasmic reticulum aminopeptidase (ERAP) 1 and 2, leucyl and cystinyl aminopeptidase (LNPEP) and aminopeptidase puromycin sensitive (NPEPPS) genes. (From Chen et al. 2017, pubmed:28259985.)

Studies have suggested that a predominant shared component, including the HLA-B allele HLA-B27, predisposes to all phenotypic subsets, and that these subsets should be considered as various phenotypic expressions of the same disease (Said-Nahal et al. 2000, pubmed:10857795; Said-Nahal et al. 2001, pubmed:11762681). [from MIM:106300, 2020.02.25]