Increased levels of antiviral MxA protein in peripheral blood of patients with A chronic disease of unknown etiology*

Abstract

Interferon alpha (IFN-alpha) is synthesized in response to viral infections. MxA protein, induced specifically by IFN-alpha and beta, expressed in peripheral blood cells, is detected more consistently than circulating IFN-alpha in serum of patients with viral infections. Thus, activation of the IFN-alpha/MxA system can be used as additional marker of the presence of a virus in patients. Therefore MxA protein and IFN-alpha levels were measured in patients with multiple sclerosis (MS), a chronic neurological disease of unknown etiology, in order to investigate the possible role of viruses in the expression of this disease. The means of MxA values obtained by using an immunochemiluminescent assay were significantly higher in blood of patients with remitting (n = 197) or relapsing (n = 39) multiple sclerosis (MS) patients and in patients with viral infections than in blood from healthy controls (n = 25) and from patients with bacterial infections (n = 12). Intra-individual variance in MxA levels in seven clinically stable remitting patients with MS was observed in the course of a follow-up, and high MxA levels were detected in three of them in blood samples collected consecutively over several months. By using an ultra sensitive assay, a higher MxA-inducer activity was obtained with sera from MS patients (n = 39) than with those from healthy controls (n = 12). Experiments with neutralizing antibodies proved that this activity in serum from patients was due to IFN-alpha, whereas IFN-alpha could not be detected by other methods. Altogether these results demonstrate that there is an activation of the IFN-alpha/MxA system in MS patients, which is consistent with the hypothesis that a viral infection may be associated with MS.

Pharmacodynamics of interferon beta in multiple sclerosis patients with or without serum neutralizing antibodies

“…This finding is not new and is most likely due to heterogeneity in the immunology of patients with MS. Indeed, Chieux and co-authors [37] reported that, in contrast to moderate differences in MxA expression in healthy individuals, clinically ability, including the immunological (e.g. change in Th1/Th2 ratio or cross-talk from other cytokineactivated pathways) and genetic characteristics of patients [38][39][40][41].…”

Single nucleotide polymorphisms and functional analysis of MxA promoter region in multiple sclerosis

“…Thus, our findings lead to the hypothesis that MS patients with − 88T haplotype express much higher levels of MxA protein in response to IFNs, and those who have − 123A express MxA in high levels without IFNs. Chieux et al [9] have demonstrated increased levels of MxA protein in MS without IFN injection. They speculated that the higher levels of MxA resulted from activation of the whole IFN-MxA system via viral infection.…”

A subtype of multiple sclerosis defined by an activated immune defense program

“…28 The increased expression of MxA confirms data from a previous report that also showed increased expression of MxA at the protein level in PB cells of RRMS patients. 29 Accordingly, Chieux et al 29 also showed increased levels of IFN-a in the serum of MS patients.…”