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EBioMedicine. 2016 Apr;6:190-198. doi: 10.1016/j.ebiom.2016.03.001. Epub 2016 Mar 10.

Human Endogenous Retrovirus and Neuroinflammation in Chronic Inflammatory Demyelinating Polyradiculoneuropathy.

Author information

1
GeNeuro Innovation, France.
2
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.
3
Department of Clinical Neuroscience, Lausanne University Hospital (CHUV), Switzerland.
4
Department of Neurology, Henri Mondor Hospital, APHP, Université Paris Est, Créteil, France.
5
GeNeuro SA, (Geneva), Switzerland.
6
GeNeuro Innovation, France; GeNeuro SA, (Geneva), Switzerland. Electronic address: hp@geneuro.com.

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.

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.

KEYWORDS:

CIDP; Endogenous retrovirus; GNbAC1; HERV; HERV-W; MSRV; Peripheral neuropathies; Schwann cell

PMID:
27211560
PMCID:
PMC4856744
DOI:
10.1016/j.ebiom.2016.03.001
[Indexed for MEDLINE]
Free PMC Article

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