The pathogenesis of axial spondyloarthritis (axSpA), although not entirely clear yet, is largely based on genes, the strongest association being with HLA-B27, importantly also in connection with aminopeptidase ERAP 1 polymorphisms. Peptides potentially derived from microbes and/or autoantigens presented by HLA-B27 expressed on antigen-presenting cells to CD8+T cells are thought to play a critical role. Studies in HLA-B27 positive patients with AS and reactive arthritis over the last decades have pointed towards a clonal expansion of CD8+T cells with similar and shared T cell receptors (TCR) suggestive of binding antigens with a common motif. This offers the therapeutic option of inhibiting or eliminating selected TCR. Indeed, a recent report on an axSpA patient who was treated with an antibody to the TCR TRBV9 has suggested that this intervention may be successful.

Radiographic axial spondyloarthritis (axSpA), which is largely equivalent to ankylosing spondylitis (AS), is a frequent inflammatory musculoskeletal rheumatic disease that affects the axial skeleton, peripheral joints, entheses and the anterior uvea by inflammation and new bone formation in the spine.1 2 AS is highly heritable with a definite genetic background attributed to the strong association with a molecule of the major histocompatibility complex (MHC), the human leucocyte antigen (HLA)-B27.3–7 The pathogenetic and clinical relevance of this genetic association that is quite unique in medicine has been recently highlighted in reviews.8 9 The mortality of AS patients is increased due to disease activity and cardiovascular morbidity,10 11 but HLA B27 is not a risk factor for mortality in the population.12

The human MHC is a large locus on DNA containing a set of closely linked polymorphic HLA genes that code for cell surface proteins, which are essential for the adaptive immune system. The MHC gene family is divided into three classes I, II and III. …