Macrophage migration inhibitory factor may contribute to vasculopathy in systemic sclerosis

Abstract

Increasing evidence supports the concept of macrophage migration inhibitory factor (MIF) as a central proinflammatory cytokine in autoimmune diseases. To further evaluate its role in systemic sclerosis (SSc), serum levels of MIF were determined by enzyme-linked immunoassay, and correlations to clinical manifestations were analyzed in 43 patients. MIF levels were significantly increased in patients (median, 18.8; range, <0.015-189 ng/ml) in comparison to healthy controls (n=43, 8.0, <0.015-36.5 ng/ml; P<0.0005). MIF values were higher in diffuse than in limited cutaneous SSc (P<0.005). Patients with pulmonary hypertension and recurrent digital ulcers showed higher MIF levels than patients without these manifestations (P<0.005). This association was also observed in limited cutaneous SSc. Sequential studies revealed decreased MIF levels after initiation of immunosuppressive therapy. MIF levels were not significantly different in patients with and without macrovascular disease of the peripheral arteries. The results suggest that MIF might contribute to inflammation and vasculopathy in SSc.

Analysis of serum macrophage migration inhibitory factor and D‐dopachrome tautomerase in systemic sclerosis

“…Here, we examined concentrations of serum MIF and DDT in SSc and HC, in order to determine their clinical associations in SSc. In line with previous studies,9, 15 we found a significant increase in serum MIF concentrations in SSc patients compared to HC. However, there was no significant difference in serum DDT between SSc and HC.…”

“…However, whether this is the case in our data is not established and we found no significant correlation between serum MIF concentrations and mRSS in patients with diffuse SSc. The absence of differences in serum MIF according to other clinical parameters in SSc is in line with one previous study,14 but conflicts with other studies which have reported higher serum MIF in patients with diffuse SSc, PAH or digital ulcers 9, 10. The small size of these vascular phenotypic subsets in our study may explain these discrepancies.…”

“…The small size of these vascular phenotypic subsets in our study may explain these discrepancies. Moreover, Becker et al ., who found an association between high MIF levels and PAH, defined PAH primarily on the basis of TTE rather than RHC and therefore described a higher proportion of patients with PAH in their cohort than usually reported 9. The cohort examined in our study is notable for a low prevalence of PAH (4%).…”

An MIF Promoter Polymorphism Is Associated with Susceptibility to Pulmonary Arterial Hypertension in Diffuse Cutaneous Systemic Sclerosis

“…Interestingly, elevated protein levels of this gene have been detected in the sera of dcSSc patients affected by PAH [13,21]. Moreover, Le Hiress et al showed through in vitro studies that MIF receptor (CD74) is overexpressed in individuals with idiopathic PAH [22].…”

“…Interestingly, increased MIF protein levels have been reported in patients with idiopathic pulmonary fibrosis, pulmonary hypertension, and in individuals affected by SSc-associated PAH [11][12][13].…”