Aetiology and pathogenesis of reactive arthritis: role of non-antigen-presenting effects of HLA-B27

The association between a group of rheumatic diseases called spondyloarthropathies (SpA) and human leukocyte antigen (HLA)-B27 has been known for several decades [1,2]. Several theories have been proposed to clarify the pathogenic role of HLA-B27 [3-7], many of them based on the idea that classical function of HLA-B27, antigen presentation to T cells, is somehow abnormal and leads to the development of inflammatory diseases. However, the proposed theories about altered antigen presenting effects of HLA-B27 have not yielded a widely accepted and comprehensive explanation of the association of HLA-B27 and SpA.Reactive arthritis (ReA) is an acute inflammatory joint disease belonging to the group of SpA. The term ReA was originally introduced to define a sterile joint inflammation during or after infection elsewhere in the body [8]. The definition was later changed because bacterial antigens and nucleic acids from the causative bacteria were found in the inflamed joints [9-11]. Today ReA is defined as an asymmetrical inflammatory oligoarthritis or monoarthritis predominantly affecting the lower limbs [12], but no established criteria for the diagnosis of ReA are available [13,14]. It is triggered by infection, most often in the gut or in the urogenital tract by various facultative or obligate intracellular Gram-negative bacteria such as Salmonella (different serotypes), Yersinia enterocolitica, Yersinia pseudotuberculosis, Shigella flexneri, Shigella sonnei, Campylobacter jejuni, Chlamydia trachomatis or Chlamydia pneumoniae [9,15,16].Recent studies suggest that in addition to its function as an antigen-presenting molecule, HLA-B27 might also have other functions that could modulate the inflammatory response and thus might cause susceptibility to SpA. Results from these experiments have offered new information about the abnormal host–microbe interaction between ReA-triggering bacteria and an HLA-B27-positive host [17-19]. In this review we summarize the data obtained fr