title: Natalizumab inhibits the expression of human endogenous retroviruses of the W family in multiple sclerosis patients: a longitudinal cohort study.
abstract: BACKGROUND
  Several viruses were reported as co-factors triggering the pathogenesis of multiple sclerosis (MS), including the endogenous retroviruses of the HERV-W family, that were also proposed as biomarkers of disease progression and therapy outcome.
  
  
  OBJECTIVE
  The objective of this article is to clarify whether in MS patients treatment with natalizumab has effects on MSRV/syncytin-1/HERV-W expression and the possible relationship with disease outcome.
  
  
  METHODS
  Peripheral blood mononuclear cells were collected from 22 patients with relapsing-remitting disease, at entry and after three, six and 12 months of treatment with natalizumab. The cell subpopulations and the expression of MSRVenv/syncytin-1/HERV-Wenv were analyzed by flow cytometry and by discriminatory env-specific RT-PCR assays.
  
  
  RESULTS
  By flow cytometry the relative amounts of T, NK and monocyte subpopulations were shown to remain fairly constant. A relative increase of B lymphocytes was observed at three to six months (p = 0.033). The MSRVenv and syncitin-1 transcripts were reduced at six to 12 months of therapy (p = 0.0001). Accordingly, at month 12, the plasma-membrane levels of the HERV-Wenv protein were reduced (p = 0.0001). B cells, NK and monocytes but not T cells expressed the HERV-Wenv protein. None of the patients relapsed during therapy.
  
  
  CONCLUSIONS
  Effective therapy with natalizumab downregulates MSRV/syncytin-1/HERV-W expression.
authors.affiliation: Department of Clinical and Experimental Medicine, University of Sassari, Italy.
authors.forename: Giannina
authors.initials: G
authors.lastname: Arru
authors.forename: Stefania
authors.initials: S
authors.lastname: Leoni
authors.forename: Maura
authors.initials: M
authors.lastname: Pugliatti
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mei
authors.forename: Caterina
authors.initials: C
authors.lastname: Serra
authors.forename: Lucia Gemma
authors.initials: LG
authors.lastname: Delogu
authors.forename: Roberto
authors.initials: R
authors.lastname: Manetti
authors.forename: Antonina
authors.initials: A
authors.lastname: Dolei
authors.forename: Stefano
authors.initials: S
authors.lastname: Sotgiu
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Mameli
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D015331:Cohort Studies; D020077:Endogenous Retroviruses / Q000187:drug effects*; D005260:Female; D005434:Flow Cytometry; D015686:Gene Products, env / Q000032:analysis*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000821:virology*; D000069442:Natalizumab; D011257:Pregnancy Proteins / Q000032:analysis*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D015686:Gene Products, env; D000069442:Natalizumab; D011257:Pregnancy Proteins; C405335:syncytin
keywords: MSRV/syncytin-1/HERV-W; Multiple sclerosis; natalizumab