Human Endogenous Retrovirus and Neuroinflammation in Chronic Inflammatory Demyelinating Polyradiculoneuropathy.

Détails

Ressource 1Télécharger: BIB_21632FCF890F.P001.pdf (1134.38 [Ko])
Etat: Public
Version: de l'auteur⸱e
ID Serval
serval:BIB_21632FCF890F
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Human Endogenous Retrovirus and Neuroinflammation in Chronic Inflammatory Demyelinating Polyradiculoneuropathy.
Périodique
EBioMedicine
Auteur⸱e⸱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
Statut éditorial
Publié
Date de publication
04/2016
Peer-reviewed
Oui
Volume
6
Pages
190-198
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
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.

Mots-clé
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
Oui
Création de la notice
06/06/2016 16:20
Dernière modification de la notice
20/08/2019 12:57
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