Human Endogenous Retrovirus and Neuroinflammation in Chronic Inflammatory Demyelinating Polyradiculoneuropathy.

Autor:	Faucard R; GeNeuro Innovation, France., Madeira A; GeNeuro Innovation, France., Gehin N; GeNeuro Innovation, France., Authier FJ; Reference Center for Neuromuscular Diseases, Department of Pathology, Henri Mondor Hospital, Créteil, France; INSERM U955-Team 10 Biology of the Neuromuscular System, Paris Est-Creteil University, Créteil, France., Panaite PA; Department of Clinical Neuroscience, Lausanne University Hospital (CHUV), Switzerland., Lesage C; Department of Neurology, Henri Mondor Hospital, APHP, Université Paris Est, Créteil, France., Burgelin I; GeNeuro SA, (Geneva), Switzerland., Bertel M; GeNeuro Innovation, France., Bernard C; GeNeuro SA, (Geneva), Switzerland., Curtin F; GeNeuro SA, (Geneva), Switzerland., Lang AB; GeNeuro SA, (Geneva), Switzerland., Steck AJ; Department of Clinical Neuroscience, Lausanne University Hospital (CHUV), Switzerland., Perron H; GeNeuro Innovation, France; GeNeuro SA, (Geneva), Switzerland. Electronic address: hp@geneuro.com., Kuntzer T; Department of Clinical Neuroscience, Lausanne University Hospital (CHUV), Switzerland., Créange A; Department of Neurology, Henri Mondor Hospital, APHP, Université Paris Est, Créteil, France.
Jazyk:	angličtina
Zdroj:	EBioMedicine [EBioMedicine] 2016 Apr; Vol. 6, pp. 190-198. Date of Electronic Publication: 2016 Mar 10.
DOI:	10.1016/j.ebiom.2016.03.001
Abstrakt:	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. 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). 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. 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. Funding: Geneuro-Innovation, France. (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze:	MEDLINE
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