BACKGROUND AND PURPOSE: Recombinant interferon-beta is proven as an effective long-term treatment in patients with multiple sclerosis (MS). Unlike in other chronic inflammatory diseases, endogenous synthesis of type I interferons (IFN-alpha and IFN-beta) has not been studied extensively in MS. Mx proteins A and B (MxA and MxB) are intracellular proteins that are induced exclusively by type I IFNs. We investigated the expression of Mx proteins in post-mortem brain tissue of IFN-beta-naïve MS patients as a marker for endogenous synthesis of type I IFNs. METHODS: By employing monoclonal antibodies specific for MxA and MxB positive staining was detectable predominantly in reactive astrocytes within the MS plaques but also in endothelial and ependymal cells as well as in lymphocytic infiltrates. RESULTS: This is of interest in view of results previously published by our group and others that Mx protein concentrations measured by ELISA increase in blood samples from MS patients after IFN-beta therapy. CONCLUSIONS: In MS, Mx proteins are detectable in plaques suggesting endogenous synthesis of type I IFNs as part of the acute inflammatory process.
BACKGROUND AND PURPOSE: Recombinant interferon-beta is proven as an effective long-term treatment in patients with multiple sclerosis (MS). Unlike in other chronic inflammatory diseases, endogenous synthesis of type I interferons (IFN-alpha and IFN-beta) has not been studied extensively in MS. Mx proteins A and B (MxA and MxB) are intracellular proteins that are induced exclusively by type I IFNs. We investigated the expression of Mx proteins in post-mortem brain tissue of IFN-beta-naïve MS patients as a marker for endogenous synthesis of type I IFNs. METHODS: By employing monoclonal antibodies specific for MxA and MxB positive staining was detectable predominantly in reactive astrocytes within the MS plaques but also in endothelial and ependymal cells as well as in lymphocytic infiltrates. RESULTS: This is of interest in view of results previously published by our group and others that Mx protein concentrations measured by ELISA increase in blood samples from MS patients after IFN-beta therapy. CONCLUSIONS: In MS, Mx proteins are detectable in plaques suggesting endogenous synthesis of type I IFNs as part of the acute inflammatory process.
Authors: Eline M E Coerver; Eva M M Strijbis; Laura F Petzold; Zoé L E Van Kempen; Bas Jasperse; Frederik Barkhof; Cees B M Oudejans; Bernard M J Uitdehaag; Charlotte E Teunissen; Joep Killestein Journal: Front Neurol Date: 2022-08-17 Impact factor: 4.086