System; Sclerosis Clinical Trial
Official title:
Role of Macrophage Migratory Inhibitory Factor in Systemic Sclerosis
Migration Inhibitory Factor has proliferative and antiapoptotic actions on fibroblasts which may be relevant to scleroderma because of the central role of a dysregulated fibroproliferative response in disease-affected tissues
- Systemic sclerosis (scleroderma) is a disease of unknown etiology characterized by fibrosis of the skin and internal organs, pronounced vasculopathy, and dysregulated immune system. - Clinically, the disease is divided into 2 major subsets, diffuse cutaneous SSc (dcSSc) and limited cutaneous SSc (lcSSc). The diffuse cutaneous subtype is generally associated with significant internal organ involvement, especially renal crisis and diffuse alveolitis of the lung, along with antitopoisomerase (antitopo) autoantibody. The limited cutaneous subtype is distinguished by Raynaud's phenomenon, telangiectasias, pulmonary hypertension, and the presence of anticentromere antibody. However, there is significant overlap both in the clinical manifestations and in the specific autoantibodies that occur in these subtypes. It is not known what predisposes a susceptible individual to develop one subtype versus another, nor is there significant information about how the 2 disease subtypes may be pathogenically related. - Activation of T lymphocytes and macrophages is an early event in the parthenogenesis of SSc. Activated T cells , macrophages and endothelial cells are important sources of Macrophage Migration Inhibitory Factor MIF was initially identified as the protein secreted by activated T lymphocytes capable of inhibiting random migration of macrophages, concentrating macrophages at inflammation loci, and enhancing their ability to kill intracellular parasites and tumoral cells. - Migration Inhibitory Factor has proliferative and antiapoptotic actions on fibroblasts which may be relevant to scleroderma because of the central role of a dysregulated fibroproliferative response in disease-affected tissues. - In patients with SSc, elevated serum levels of MIF, increased MIF expression in the skin and afunctional promoter polymorphism in the MIF gene that might influence clinical expression have been described therefore MIF might have an important role in the disease. ;
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