Ankylosing Spondylitis

Ankylosing spondylitis (AS) is a chronic, progressive inflammatory spondyloarthropathy with a strong genetic association to HLA-B27 (present in >90% of AS patients, though only 5-6% of HLA-B27-positive individuals develop AS). The disease primarily targets the axial skeleton, beginning at the sacroiliac joints and ascending the spine. The pathogenesis involves aberrant immune activation at entheses — the sites where tendons, ligaments, and joint capsules insert into bone. HLA-B27 may contribute through the arthritogenic peptide hypothesis (presenting self-peptides that trigger autoreactive CD8+ T-cells), misfolding in the endoplasmic reticulum triggering IL-23/IL-17 inflammatory pathways, or forming homodimers recognized by natural killer cells. IL-17 and TNF-alpha are the dominant cytokines driving enthesitis and synovitis. Chronic inflammation at entheses leads to erosive bone destruction followed by aberrant new bone formation (syndesmophytes) through activation of BMP and Wnt signaling pathways. Progressive syndesmophyte formation bridges adjacent vertebral bodies, creating the characteristic 'bamboo spine' appearance on X-ray. The process also affects the sacroiliac joints (sacroiliitis — the earliest radiographic finding), peripheral joints (asymmetric oligoarthritis of large joints), and extra-articular sites including the anterior uvea (acute anterior uveitis in 25-40%),...