HLA-B27 as a potential target for the cure of axial spondyloarthritis

Axial spondyloarthritis (axSpA) manifests with inflammatory back pain and is diagnosed predominantly in subjects carrying the human leucocyte antigen (HLA)-B27 allele. While not diagnostic for the disease or a predictive biomarker in the general population, there is convincing data on the pathogenic role of HLA-B27 in axSpA via different proinflammatory mechanisms. Similar to other chronic conditions, axSpA requires lifelong treatments, including biologics and small molecules, to treat inflammation and ultimately halt disease progression by achieving sustained disease remission. There is currently no cure for axSpA, but one fascinating thesis is that gene therapy may hold the potential to reverse the disease. We provide herein a comprehensive and critical review of the advances in gene therapy strategies, including gene-editing techniques, RNA interference, and viral vector–mediated delivery systems, with a focus on the possible future developments in HLA-B27-related mechanisms. Understanding these novel approaches may pave the way for more effective, personalized treatments capable of solving the HLA-B27-positive axSpA conundrum.