Natalizumab inhibits the expression of human endogenous retroviruses of the W family in multiple sclerosis patients: a longitudinal cohort study

Mult Scler. 2014 Feb;20(2):174-82. doi: 10.1177/1352458513494957. Epub 2013 Jul 22.

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.

Conclusion: Effective therapy with natalizumab downregulates MSRV/syncytin-1/HERV-W expression.

Keywords: MSRV/syncytin-1/HERV-W; Multiple sclerosis; natalizumab.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Cohort Studies
  • Endogenous Retroviruses / drug effects*
  • Female
  • Flow Cytometry
  • Gene Products, env / analysis*
  • Humans
  • Leukocytes, Mononuclear / virology
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy*
  • Multiple Sclerosis, Relapsing-Remitting / virology*
  • Natalizumab
  • Pregnancy Proteins / analysis*
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Young Adult

Substances

  • Antibodies, Monoclonal, Humanized
  • Gene Products, env
  • Natalizumab
  • Pregnancy Proteins
  • syncytin