Sequence of Events in the Pathogenesis of Axial Spondyloarthritis: A Current Review—2023 SPARTAN Meeting Proceedings

Purpose of Review Over the past two decades, significant progress has been made to untangle the etiology of inflammation and new bone formation (NBF) associated with axial spondyloarthritis (axSpA). However, exact mechanisms as to how the disease initiates and develops remain elusive. Recent Findings Type 3 immunity, centered around the IL-23/IL-17 axis, has been recognized as a key player in the pathogenesis of axSpA. Multiple hypotheses associated with HLA-B*27 have been proposed to account for disease onset and progression of axSpA, potentially by driving downstream T cell responses. However, HLA-B*27 alone is not sufficient to fully explain the development of axSpA. Genome-wide association studies (GWAS) identified several genes that are potentially relevant to disease pathogenesis leading to a better understanding of the immune activation seen in axSpA. Furthermore, gut microbiome studies suggest an altered microbiome in axSpA, and animal studies suggest a pathogenic role for immune cells migrating from the gut to the joint. Recent studies focusing on the pathogenesis of new bone formation (NBF) have highlighted the importance of endochondral ossification, mechanical stress, pre-existing inflammation, and activated anabolic signaling pathways during the development of NBF. Summary Despite the complex etiology of axSpA, recent studies have shed light on pivotal pieces that could lead to a better understanding of the pathogenic events in axSpA.