Seronegative Spondyloarthritis: Epidemiology, Pathogenesis, And Pathology

Abstract

Classification of spondyloarthritis (SpA) is aimed at including patients with radiographic evidence of sacroiliitis and those with early disease who do not yet meet radiographic criteria but have positive features on magnetic resonance imaging (MRI). Most studies report a prevalence of SpA of 0.1 to 0.6%. Human leukocyte antigen (HLA)-B27 contributes approximately 20% of the heritability of SpA, and non–major histocompatibility complex loci identified to date (n = 113) contribute another approximately 10%. To date, 160 subtypes of HLA-B*27 have been reported, although population-based disease association studies are limited to only a few subtypes. Subtypes HLA-B*27:05 and HLA-B*27:04 are examples of subtypes associated with disease, whereas HLA-B*27:06 and HLA-B*27:09 are nonassociated. Properties of the B27 molecule relevant to pathogenesis include antigen presentation, propensity to misfold, and formation of homodimers. Key pathways identified by genetic studies include the interleukin (IL)-23 and M1-aminopeptidase pathways. The latter pathway is involved in peptide trimming in the endoplasmic reticulum, changing both the length and amino acid composition of peptides available for HLA class I presentation. IL-23 is a key cytokine regulating expression of IL-17 in a specific T helper cell phenotype, Th17, and also a variety of cells of the innate immune system. The IL-23–IL-17 pathway has been directly implicated in inflammation at sites that are inflamed in SpA. Increasing evidence based on prospective clinical and imaging data supports a link between inflammation and ankylosis, especially if the resolution of inflammation is followed by the appearance of a particular type of reparative tissue, namely, fat metaplasia, on T1-weighted MRI. This review contains 8 figures, 5 tables and 33 references Key words: association, classification, genetics, heritability, innate immunity, prevalence, spondyloarthritis