Ankylosing spondylitis: An overview of pathophysiology and therapeutic landscape

Abstract

Ankylosing spondylitis (AS) is a chronic inflammatory autoimmune disease belonging to a group of conditions called spondyloarthritis that predominantly affects the spine and lower back joints. It is characterized by inflammation in the spine, stiffness in sacroiliac joints and progressive loss of mobility. The precise etiology of the disease remains unknown. Current hypotheses regarding the pathogenesis of AS suggest that multiple mechanisms are involved in its development. The genetic predisposition linked to HLA-B*27 represents the earliest documented finding; approximately five decades ago, extensive research indicated that it is not the sole factor responsible for the onset of the disease. New insights have been reported into the role of non-MHC genes, molecular mimicry, the generation of arthritogenic peptides, misfolded HLA-B*27 dimers or oligomers, and immune dysregulation. Two major hallmarks of this immune-mediated disease are inflammation and abnormal bone formation; both serve as targets for current therapies. Advances in the understanding of its pathophysiology have led to the development of highly effective and targeted treatment. AS treatments encompass NSAIDs, biologics (such as tumour necrosis factor inhibitors, interleukin-17 inhibitors, and interleukin-23 inhibitors), both conventional and targeted synthetic DMARDs, as well as monoclonal antibody therapies. The present study aims to provide a comprehensive overview of the pathophysiology, genetic and immunological factors involved in the process, as well as therapeutic advances reported in recent years.