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Human Endogenous Retrovirus and Neuroinflammation in Chronic Inflammatory Demyelinating Polyradiculoneuropathy.
- Source :
-
EBioMedicine [EBioMedicine] 2016 Apr; Vol. 6, pp. 190-198. Date of Electronic Publication: 2016 Mar 10. - Publication Year :
- 2016
-
Abstract
- Background: Human endogenous retroviruses HERV-W encode a pro-inflammatory protein, named MSRV-Env from its original identification in Multiple Sclerosis. Though not detected in various neurological controls, MSRV-Env was found in patients with chronic inflammatory demyelinating polyradiculoneuropathies (CIDPs). This study investigated the expression of MSRV in CIDP and evaluated relevant MSRV-Env pathogenic effects.<br />Methods: 50 CIDP patients, 19 other neurological controls (ONDs) and 65 healthy blood donors (HBDs) were recruited from two different countries. MSRV-env and -pol transcripts, IL6 and CXCL10 levels were quantified from blood samples. MSRV-Env immunohistology was performed in distal sensory nerves from CIDP and neurological controls biopsies. MSRV-Env pathogenic effects and mode of action were assayed in cultured primary human Schwann cells (HSCs).<br />Findings: In both cohorts, MSRV-env and -pol transcripts, IL6 positivity prevalence and CXCL10 levels were significantly elevated in CIDP patients when compared to HBDs and ONDs (statistically significant in all comparisons). MSRV-Env protein was detected in Schwann cells in 5/7 CIDP biopsies. HSC exposed to or transfected with MSRV-env presented a strong increase of IL6 and CXCL10 transcripts and protein secretion. These pathogenic effects on HSC were inhibited by GNbAC1, a highly specific and neutralizing humanized monoclonal antibody targeting MSRV-Env.<br />Interpretation: The present study showed that MSRV-Env may trigger the release of critical immune mediators proposed as instrumental factors involved in the pathophysiology of CIDP. Significant MSRV-Env expression was detected in a significant proportion of patients with CIDP, in which it may play a role according to its presently observed effects on Schwann cells along with previously known effects on immune cells. Experimental results also suggest that a biomarker-driven therapeutic strategy targeting this protein with a neutralizing antibody such as GNbAC1 may offer new perspectives for treating CIDP patients with positive detection of MSRV-Env expression.<br />Funding: Geneuro-Innovation, France.<br /> (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)
- Subjects :
- Adult
Aged
Antibodies, Monoclonal, Humanized pharmacology
Cell Line
Endogenous Retroviruses genetics
Endogenous Retroviruses immunology
Female
France
Gene Products, pol genetics
Humans
Male
Middle Aged
Polyradiculoneuropathy, Chronic Inflammatory Demyelinating genetics
Polyradiculoneuropathy, Chronic Inflammatory Demyelinating virology
Schwann Cells drug effects
Schwann Cells virology
Young Adult
Chemokine CXCL10 genetics
Endogenous Retroviruses pathogenicity
Gene Products, env genetics
Interleukin-6 genetics
Polyradiculoneuropathy, Chronic Inflammatory Demyelinating immunology
Subjects
Details
- Language :
- English
- ISSN :
- 2352-3964
- Volume :
- 6
- Database :
- MEDLINE
- Journal :
- EBioMedicine
- Publication Type :
- Academic Journal
- Accession number :
- 27211560
- Full Text :
- https://doi.org/10.1016/j.ebiom.2016.03.001