Epigenetic Landscape of Ankylosing Spondylitis: Mechanisms, Biomarkers, and Therapeutic Implications

Abstract

Back pain, stiffness, uveitis, and peripheral arthritis are the main symptoms of ankylosing spondylitis (AS), a chronic inflammatory disease of the spondyloarthritis group that affects the spine and sacroiliac joints. Early identification is crucial since progressive illness can lead to spinal fusion and functional impairment. Even though AS and the human leukocyte antigen HLA-B27 are highly heritable, the pathophysiology of the disease cannot be entirely explained by genetic predisposition alone. A growing body of research identifies epigenetic pathways as important modulators connecting immunological dysregulation and HLA-B27-associated vulnerability. DNA methylation, histone modifications, and non-coding RNA expression are examples of epigenetic mechanisms that control tissue remodelling, immune cell differentiation, and the expression of inflammatory genes. Promoter hypermethylation is typically linked to gene suppression, while hypomethylation may allow gene activation, according to transcriptomic and epigenomic research, suggesting their potential as diagnostic indicators. Chromatin accessibility and disease-related gene expression are further influenced by histone modifications such as H3K9 acetylation. Combining genetic and epigenetic knowledge improves our understanding of the pathophysiology of AS and facilitates the development of improved diagnostic and treatment approaches.