TY - JOUR
T1 - Macrophage Migration Inhibitory Factor Induces Inflammation and Predicts Spinal Progression in Ankylosing Spondylitis
AU - Guggino, Giuliana
AU - Ciccia, Francesco
AU - Haroon, Nigil
AU - Gracey, Eric
AU - Ranganathan, Vidya
AU - Sari, Ismail
AU - Zeng, Fanxing
AU - Muralitharan, Janogini
PY - 2017
Y1 - 2017
N2 - Objective: To investigate the role of macrophage migration inhibitory factor (MIF) in the pathogenesis of ankylosing spondylitis (AS). Methods: Patients who met the modified New York criteria for AS were recruited for the study. Healthy volunteers, rheumatoid arthritis patients, and osteoarthritis patients were included as controls. Based on the annual rate of increase in modified Stoke AS Spine Score (mSASSS), AS patients were classified as progressors or nonprogressors. MIF levels in serum and synovial fluid were quantitated by enzyme-linked immunosorbent assay. Predictors of AS progression were evaluated using logistic regression analysis. Immunohistochemical analysis of ileal tissue was performed to identify MIF-producing cells. Flow cytometry was used to identify MIF-producing subsets, expression patterns of the MIF receptor (CD74), and MIF-induced tumor necrosis factor (TNF) 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 healthy controls and were 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 TNF production in monocytes, activated β-catenin in osteoblasts, and promoted the mineralization of osteoblasts. Conclusion: Our findings indicate an unexplored pathogenic role of MIF in AS and a link between inflammation and new bone formation.
AB - Objective: To investigate the role of macrophage migration inhibitory factor (MIF) in the pathogenesis of ankylosing spondylitis (AS). Methods: Patients who met the modified New York criteria for AS were recruited for the study. Healthy volunteers, rheumatoid arthritis patients, and osteoarthritis patients were included as controls. Based on the annual rate of increase in modified Stoke AS Spine Score (mSASSS), AS patients were classified as progressors or nonprogressors. MIF levels in serum and synovial fluid were quantitated by enzyme-linked immunosorbent assay. Predictors of AS progression were evaluated using logistic regression analysis. Immunohistochemical analysis of ileal tissue was performed to identify MIF-producing cells. Flow cytometry was used to identify MIF-producing subsets, expression patterns of the MIF receptor (CD74), and MIF-induced tumor necrosis factor (TNF) 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 healthy controls and were 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 TNF production in monocytes, activated β-catenin in osteoblasts, and promoted the mineralization of osteoblasts. Conclusion: Our findings indicate an unexplored pathogenic role of MIF in AS and a link between inflammation and new bone formation.
KW - Adult; Antigens
KW - Ankylosing; Synovial Fluid; Tumor Necrosis Factor-alpha; Disease Progression; Immunology and Allergy; Rheumatology; Immunology
KW - B-Lymphocyte; Calcification
KW - Differentiation
KW - Physiologic; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Female; Histocompatibility Antigens Class II; Humans; Intramolecular Oxidoreductases; Logistic Models; Macrophage Migration-Inhibitory Factors; Macrophages; Male; Middle Aged; Monocytes
KW - Adult; Antigens
KW - Ankylosing; Synovial Fluid; Tumor Necrosis Factor-alpha; Disease Progression; Immunology and Allergy; Rheumatology; Immunology
KW - B-Lymphocyte; Calcification
KW - Differentiation
KW - Physiologic; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Female; Histocompatibility Antigens Class II; Humans; Intramolecular Oxidoreductases; Logistic Models; Macrophage Migration-Inhibitory Factors; Macrophages; Male; Middle Aged; Monocytes
UR - http://hdl.handle.net/10447/245718
UR - https://onlinelibrary.wiley.com/doi/full/10.1002/art.40175
M3 - Article
VL - 69
SP - 1796
EP - 1806
JO - ARTHRITIS & RHEUMATOLOGY
JF - ARTHRITIS & RHEUMATOLOGY
SN - 2326-5191
ER -