The link between HLA-B27 and SpA-new ideas on an old problem

The strong association of the HLA-B27 with AS was first discovered independently by groups in London and California in 1972 and has recently been confirmed beyond reasonable doubt by fine mapping in the latest and most sophisticated genome-wide association study (GWAS) published this July. Yet, despite nearly four decades of extensive research, the exact role that HLA-B27 plays in pathogenesis remains unknown. However, we believe that recent developments in three fields have allowed us to view this conundrum in a new light and to propose coherent theories of disease pathogenesis. These areas are as follows: (i) GWASs, (ii) studies of B27 biology and (iii) lessons from biologic therapies. In this review we will discuss these recent advances before discussing the current models of AS pathogenesis under investigation.