Targeting HLA-B27 Misfolding as a Potential Therapeutic Treatment of Ankylosying spondylitis

Human Leucocyte Antigen (HLA)-B27 associated inflammatory arthritic diseases, referred to as the spondyloarthropathies (SpAs) remain enigmatic. Genome wide associations scans (GWAS) have revealed other strong genetic associations with the SpAs but have yet to provide a telling insight into the cause of disease and the role of the strongest genetic marker HLA-B27. Recent observations suggest that misfolding of HLA-B27 may be a contributory factor to the development of inflammatory arthritis. Targeting aberrant conformations of HLA-B27 and/or the pathways triggered by misfolding HLA-B27 molecules may provide a window for a different form of therapeutic approach for this group of inflammatory arthritic diseases. Here I will focus on the evidence supporting a role for HLA-B27 misfolding in disease pathology and our recent studies, which have provided a rationale for why targeting unusual intracellular HLA-B27 conformations may be a potential future therapeutic approach for treating the SpAs.