title: Human Endogenous Retrovirus and Neuroinflammation in Chronic Inflammatory Demyelinating Polyradiculoneuropathy.
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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  Geneuro-Innovation, France.
authors.affiliation: GeNeuro Innovation, France.
authors.forename: Raphaël
authors.initials: R
authors.lastname: Faucard
authors.affiliation: GeNeuro Innovation, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Madeira
authors.affiliation: GeNeuro Innovation, France.
authors.forename: Nadège
authors.initials: N
authors.lastname: Gehin
authors.affiliation: 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.
authors.forename: François-Jérôme
authors.initials: FJ
authors.lastname: Authier
authors.affiliation: Department of Clinical Neuroscience, Lausanne University Hospital (CHUV), Switzerland.
authors.forename: Petrica-Adrian
authors.initials: PA
authors.lastname: Panaite
authors.affiliation: Department of Neurology, Henri Mondor Hospital, APHP, Université Paris Est, Créteil, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Lesage
authors.affiliation: GeNeuro SA, (Geneva), Switzerland.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Burgelin
authors.affiliation: GeNeuro Innovation, France.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Bertel
authors.affiliation: GeNeuro SA, (Geneva), Switzerland.
authors.forename: Corinne
authors.initials: C
authors.lastname: Bernard
authors.affiliation: GeNeuro SA, (Geneva), Switzerland.
authors.forename: François
authors.initials: F
authors.lastname: Curtin
authors.affiliation: GeNeuro SA, (Geneva), Switzerland.
authors.forename: Aloïs B
authors.initials: AB
authors.lastname: Lang
authors.affiliation: Department of Clinical Neuroscience, Lausanne University Hospital (CHUV), Switzerland.
authors.forename: Andreas J
authors.initials: AJ
authors.lastname: Steck
authors.affiliation: GeNeuro Innovation, France; GeNeuro SA, (Geneva), Switzerland. Electronic address: hp@geneuro.com.
authors.forename: Hervé
authors.initials: H
authors.lastname: Perron
authors.affiliation: Department of Clinical Neuroscience, Lausanne University Hospital (CHUV), Switzerland.
authors.forename: Thierry
authors.initials: T
authors.lastname: Kuntzer
authors.affiliation: Department of Neurology, Henri Mondor Hospital, APHP, Université Paris Est, Créteil, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Créange
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology; D002460:Cell Line; D054357:Chemokine CXCL10 / Q000235:genetics*; D020077:Endogenous Retroviruses / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D005260:Female; D005602:France; D015686:Gene Products, env / Q000235:genetics*; D015684:Gene Products, pol / Q000235:genetics; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020277:Polyradiculoneuropathy, Chronic Inflammatory Demyelinating / Q000235:genetics / Q000276:immunology* / Q000821:virology; D012583:Schwann Cells / Q000187:drug effects / Q000821:virology; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D015686:Gene Products, env; D015684:Gene Products, pol; C508600:IL6 protein, human; D015850:Interleukin-6; C581064:temelimab
keywords: CIDP; Endogenous retrovirus; GNbAC1; HERV; HERV-W; MSRV; Peripheral neuropathies; Schwann cell