Human Endogenous Retrovirus and Neuroinflammation in Chronic Inflammatory Demyelinating Polyradiculoneuropathy.

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Version: author
Serval ID
serval:BIB_21632FCF890F
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Human Endogenous Retrovirus and Neuroinflammation in Chronic Inflammatory Demyelinating Polyradiculoneuropathy.
Journal
EBioMedicine
Author(s)
Faucard R., Madeira A., Gehin N., Authier F.J., Panaite P.A., Lesage C., Burgelin I., Bertel M., Bernard C., Curtin F., Lang A.B., Steck A.J., Perron H., Kuntzer T., Créange A.
ISSN
2352-3964 (Electronic)
ISSN-L
2352-3964
Publication state
Published
Issued date
04/2016
Peer-reviewed
Oui
Volume
6
Pages
190-198
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
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.
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).
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.
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.
Geneuro-Innovation, France.

Keywords
Adult, Aged, Antibodies, Monoclonal, Humanized/pharmacology, Cell Line, Chemokine CXCL10/genetics, Endogenous Retroviruses/genetics, Endogenous Retroviruses/immunology, Endogenous Retroviruses/pathogenicity, Female, France, Gene Products, env/genetics, Gene Products, pol/genetics, Humans, Interleukin-6/genetics, Male, Middle Aged, Polyradiculoneuropathy, Chronic Inflammatory Demyelinating/genetics, Polyradiculoneuropathy, Chronic Inflammatory Demyelinating/immunology, Polyradiculoneuropathy, Chronic Inflammatory Demyelinating/virology, Schwann Cells/drug effects, Schwann Cells/virology, Young Adult
Pubmed
Open Access
Yes
Create date
06/06/2016 16:20
Last modification date
20/08/2019 12:57
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