Molecular Biomarkers and Biosensing Innovations for the Early Diagnosis of Ankylosing Spondylitis: From Molecular Mechanisms to Precision Diagnostics.
Abstract
Ankylosing spondylitis is a chronic immune-mediated, inflammatory spondyloarthropathy in which delayed diagnosis remains a major clinical challenge, particularly during the early stages when definitive structural radiographic changes may be absent. Although HLA-B27 represents the most potent genetic association with ankylosing spondylitis, its incomplete penetrance and variability limit its use as a single diagnostic biomarker. This review critically examines the molecular mechanisms underlying HLA-B27-associated disease, evaluates circulating and molecular biomarkers according to their demonstrated clinical roles and assesses the current development of biosensing technologies for their detection. Biomarkers including IL-17, IL-13, TNF-α, MMP-3, calprotectin, microRNAs, and anti-CD74 antibodies reflect complementary aspects of inflammation, immune dysregulation and tissue remodelling; however, their biological association with the disease should not be compared with validated early diagnostic performance. Emerging optical and electrochemical biosensing platforms demonstrate promising analytical sensitivity and potential for rapid and minimally invasive detection. However, much of the available biosensor research remains at the level of analytical feasibility or biomarker detection, with limited evidence demonstrating discrimination of ankylosing spondylitis from clinical controls and very limited independent clinical validation. Major translational barriers include biomarker heterogeneity, sensor standardisation, and clinical testing. Future development should focus on clinically validated multi-biomarker biosensor systems, nanomaterial-enhanced detection and machine learning-assisted analysis. Collectively, the combination of molecular biomarker research and next-generation biosensing technology can elevate diagnostic accuracy, providing early intervention and precision medicine strategies for disease assessment.
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