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Macrophage Migration Inhibitory Factor Induces Inflammation and Predicts Spinal Progression in Ankylosing Spondylitis
Vidya Ranganathan, Francesco Ciccia1, Fanxing Zeng2
1Università degli Studi di Palermo, Palermo, Italy.
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.
Insights
Macrophage migration inhibitory factor (MIF) is elevated in ankylosing spondylitis (AS) and predicts disease progression. MIF links inflammation to new bone formation in AS pathogenesis.
Area of Science:
- Immunology
- Rheumatology
- Pathogenesis
Background:
- Ankylosing spondylitis (AS) is a chronic inflammatory disease.
- The role of macrophage migration inhibitory factor (MIF) in AS pathogenesis is not fully understood.
Purpose of the Study:
- To investigate the role of MIF in the pathogenesis of ankylosing spondylitis (AS).
Main Methods:
- Quantified MIF levels in serum and synovial fluid via ELISA.
- Analyzed MIF-producing cells in ileal tissue using immunohistochemistry.
- Assessed MIF-induced TNF production and osteoblast mineralization in vitro.
Main Results:
- Serum MIF levels were elevated in AS patients and predicted disease progression.
- MIF levels were higher in synovial fluid, with MIF-producing cells enriched in the gut.
- MIF induced TNF production, activated beta-catenin in osteoblasts, and promoted mineralization.
Conclusions:
- MIF plays a significant role in AS pathogenesis.
- MIF links inflammation and new bone formation in AS.
