Upregulated expression of macrophage migration inhibitory factor, its analogue d-dopachrome tautomerase, and the cd44 receptor in peripheral cd4 t cells from clinically isolated syndrome patients with rapid conversion to clinical defined multiple sclerosis

Background and objectives: Macrophage Migration Inhibitory Factor (MIF) and DDopachrome Tautomerase (DDT) are two pleiotropic and primarily, but not exclusively, proinflammatory cytokines belonging to the MIF family of cytokines that have recently been shown to be implicated in the pathogenesis of progressive forms of human progressive Multiple Sclerosis (MS) and the experimental model counterpart in rodents. Materials and Methods: We have presently evaluated a transcriptomic analysis of the expression of MIF, DDT, their receptors CD74 and CD44, and MIF co-receptors CXCR2, CXCR4, and CXCR7 in peripheral blood of patients with Clinically Isolated Syndrome (CIS), with rapid progression to clinical defined MS. Results: Our analysis reveals that MIF, DDT, and CD44 are overexpressed in CD4+ T cells from patients with CIS, as compared to healthy controls. Accordingly, a significant overlap was observed between the genes overexpressed in CD4+ T cells from patients with CIS and the genes belonging to the MIF regulatory network. This upregulated expression appeared to be unique for CD4+T cells, as other immune cells including CD8+ T cells, B cells, and monocytes from these patients exhibited expression levels of these molecules that were superimposable to those observed in healthy controls. Conclusions: Overall, our data suggest that the overexpression MIF cytokine family signature may occur in CD4+ T cells from patients with CIS, and that this phenomenon may be implicated in the pathogenesis of the disease, offering the possibility to represent both a diagnostic marker and a therapeutic target.