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RESEARCH PRODUCT

Macrophage Migration Inhibitory Factor Induces Inflammation and Predicts Spinal Progression in Ankylosing Spondylitis

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Objectives: To understand the role of macrophage migration inhibitory factor (MIF) in the pathogenesis of Ankylosing Spondylitis (AS). Methods: AS patients satisfying the modified New York criteria were recruited for the study. Healthy volunteers, rheumatoid arthritis and osteoarthritis patients were included as controls. Based on the annual rate of increase in mSASSS scores, AS patients were classified as progressors or non-progressors. MIF levels were quantitated by ELISA in the serum and synovial fluid. Predictors of AS progression were studied by logistic regression analysis. Immunohistochemistry of ileal tissue was performed to identify MIF producing cells. Flow cytometry was used to reveal the identity of MIF producing subsets, expression patterns of the MIF receptor (CD74) and MIF-induced TNFα production in the peripheral blood. MIF induced mineralization of osteoblast cells (Saos-2) was analyzed by Alizarin red S staining and western blotting was used to quantify active β-catenin levels. Results: Baseline serum MIF levels were significantly elevated in AS patients compared to HC and found to independently predict AS progression. MIF levels were higher in the synovial fluid of AS patients and MIF producing macrophages and Paneth cells were enriched in their gut. MIF induced TNFα production in monocytes, activated β-catenin in osteoblasts and promoted their mineralization. Conclusions: The study uncovers an unexplored pathogenic role for MIF in AS and attempts to provide a link between inflammation and new bone formation. This article is protected by copyright. All rights reserved.