Axial spondyloarthritis - from inflammation to ankylosis

Abstract

Axial spondyloarthritis is a chronic inflammatory immune-mediated rheumatic disease that mainly affects the sacroiliac joints and the spine and encompasses both sub-units - ankylosing spondylitis and its preceding phase non-radiographic axial spondyloarthritis. The disease is characterized by two main immunopathological processes – chronic inflammation and pathological new bone formation, the causal relationship of which is still not fully understood. Starting as enthesopathic inflammation in the early stages, the disease progresses to ossifying enthesitis as a result of an abnormal immune response to skeletal biomechanical stress associated recurrent tissue microdamage, and a subsequent process of excessive repair and tissue remodeling. Immune-mediated inflammation manifests with a distinct skewing of differentiation towards a Th1/Th17 phenotype and an unbalanced profile of cytokine production, with cytokine dysregulation and predominance of the effects of pro-inflammatory cytokines. Molecular signaling pathways of syndesmophyte formation include bone morphogenetic protein (BMP), wingless-type like (WNT), Dickkopf-1 (Dkk-1), sclerostin, cytokines, and others. The review summarizes the current concepts regarding the pathophysiology of both pathognomonic processes for the disease – inflammation and pronounced osteoproliferation.