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Published on: April 21, 2015
Interferon-induced Mx proteins in brain tissue of multiple sclerosis patients
A N Al-Masri1, F Heidenreich, G F Walter
1Department of Clinical Immunology, Hannover Medical School, Hannover, Germany.
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.
Insights
Mx proteins indicate endogenous type I interferon (IFN) synthesis in multiple sclerosis (MS) brain plaques. This finding suggests IFN-beta plays a role in the acute inflammatory process of MS.
Area of Science:
- Neuroimmunology
- Inflammatory Diseases
- Biomarker Discovery
Background:
- Recombinant interferon-beta is a known long-term treatment for multiple sclerosis (MS).
- Endogenous type I interferon (IFN) synthesis in MS is not well-understood.
- Mx proteins (MxA and MxB) are biomarkers for type I IFN activity.
Purpose of the Study:
- Investigate Mx protein expression in MS brain tissue.
- Determine if Mx proteins can serve as markers for endogenous type I IFN synthesis in MS.
- Correlate findings with existing data on IFN-beta therapy in MS patients.
Main Methods:
- Utilized monoclonal antibodies for MxA and MxB detection.
- Examined post-mortem brain tissue from IFN-beta-naïve MS patients.
- Analyzed protein expression within MS plaques and surrounding cells.
Main Results:
- MxA and MxB proteins were detected in MS plaques.
- Positive staining was observed in reactive astrocytes, endothelial cells, ependymal cells, and lymphocytic infiltrates.
- These findings align with previous studies showing increased Mx protein levels in MS patients' blood after IFN-beta therapy.
Conclusions:
- Mx proteins are present in MS plaques, indicating endogenous type I IFN synthesis.
- This suggests a role for type I IFNs in the acute inflammatory processes of MS.
- Mx proteins may serve as valuable biomarkers for endogenous IFN activity in MS.
