Expression of macrophage migration inhibitory factor and its receptor CD74 in systemic sclerosis

Macrophage migration inhibitory factor (MIF) has been associated with the pathogenesis of several rheumatic diseases. In systemic sclerosis (SSc) it has been shown that MIF expression is dysregulated in serum and skin. However, the MIF receptor, CD74, has been poorly investigated and its potential role in the pathogenesis of SSc remains unknown. This study aimed to analyze mRNA, tissue, and serum expression of MIF and CD74 in patients with limited (lcSSc) and diffuse (dcSSc) systemic sclerosis. A case-control study in 20 SSc patients and 20 control subjects (CS) from southern México was conducted. MIF and CD74 mRNA expression levels were quantified by real-time PCR, MIF serum levels were measured by an ELISA kit, and MIF and its receptor CD74 were evaluated by immunohistochemistry of skin biopsies. MIF mRNA expression was significantly higher in CS than in SSc patients (p = 0.02), while CD74 showed no differences between patients and CS. MIF serum levels were similar between SSc patients and CS: dcSSc = 3.82 ng/ml, lcSSc = 3.57 ng/ml, and CS = 3.28 ng/ml. In skin biopsies of SSc, MIF and CD74 were enhanced in keratinocytes, while they showed decreased expression in endothelial cells. On the other hand, the staining of CD74 was high in fibroblasts of dcSSc patients. Our findings show MIF and CD74 deregulation at the transcriptional and translational levels in SSc, which might be associated with the proinflammatory process leading to tissue remodeling and excessive fibrosis in SSc.