Ankylosing Spondylitis: Popular Democratic Republic of Algeria Ministry University Department END With a view Presented by: Askri Hanadi Djaber Hana Kaddouri Hadda Othmani Maroua Before the jury composed of: President Djahra Aliboutlelis Examiner Aouimeur Meriem Supervisor Toumi Ikram Spondylitis: Etiology and Risk Factors

Abstract

Ankylosing Spondylitis (AS) is a chronic autoimmune inflammatory disease that primarily affects the axial skeleton, especially the spine and sacroiliac joints. It typically begins in young adulthood and presents as inflammatory back pain and morning stiffness that improves with movement. The disease has been recognized since ancient times by scholars such as Bechterew, Marie, and Strümpell. Its symptoms are not confined to the musculoskeletal system, as it also manifests with extra-articular features such as uveitis, inflammatory bowel disease, psoriasis, cardiovascular and pulmonary disorders, osteoporosis, and kidney diseases. It leads to restricted mobility, loss of independence, and a significant decline in quality of life, particularly in advanced stages. Genetic factors especially the presence of the HLA-B27 gene and its interaction with ERAP1 and IL-23R interact with environmental and lifestyle elements such as smoking, microbiome disturbances, and dietary habits to induce a prominent immune imbalance via the IL-23/IL-17 axis. This drives inflammation at tendon-bone attachment sites and leads to structural abnormalities. The relationship between chronic inflammation and an increased risk of certain cancers, such as hematologic malignancies and prostate cancer has become a recent research focus. This dissertation presents a comprehensive overview beginning with the anatomy and vital functions of the musculoskeletal system, followed by an exploration of the disease mechanisms, contributing factors, and recent developments in metabolomics and genome￾wide association studies (GWAS). It aims to provide a multidisciplinary perspective combining toxicology, immunology, genetics, and clinical sciences to deepen the understanding of the disease and improve patients’ quality of life.