Anti-human herpesvirus 6A/B IgG correlates with relapses and progression in multiple sclerosis

PLoS One. 2014 Aug 11;9(8):e104836. doi: 10.1371/journal.pone.0104836. eCollection 2014.

Abstract

Objective: To analyze the titers of the IgG and IgM antibodies against human herpesvirus 6A/B (HHV-6A/B) in multiple sclerosis (MS) patients treated with different disease modified therapies (DMTs) along two-years of follow-up.

Methods: We collected 2163 serum samples from 596 MS; for 301 MS patients a 2-years follow-up was performed. Serum samples of 337 healthy controls were also analyzed. Anti-HHV-6A/B IgG and IgM were analyzed by ELISA (Panbio).

Results: We found that 129/187 (69.0%) MS patients with a decrease of the anti-HHV-6A/B IgG titers after 2-years with DMTs were free of relapses and progression vs. 46/113 (40.7%) of MS patients with an increase of the anti-HHV-6A/B IgG titers (p = 0.0000015); the higher significance was found for natalizumab. Furthermore, we found that anti-HHV-6A/B IgG titers reached their highest value two weeks before the relapse (p = 0.0142), while the anti-HHV-6A/B IgM titers reached their highest value one month before the relapse (p = 0.0344).

Conclusion: The measurement of the anti-HHV-6A/B IgG titers could be a good biomarker of clinical response to the different DMTs. The increase of the anti-HHV-6A/B IgG and IgM titers predicts the upcoming clinical relapses. However, further longitudinal studies are needed to validate these results.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Neutralizing / blood
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / immunology*
  • Biomarkers / blood
  • Disease Progression
  • Female
  • Herpesvirus 6, Human / immunology*
  • Humans
  • Immunoglobulin G / blood*
  • Immunoglobulin G / immunology
  • Immunoglobulin M / blood*
  • Immunoglobulin M / immunology
  • Immunologic Factors / therapeutic use
  • Interferon-beta / immunology
  • Male
  • Multiple Sclerosis / blood
  • Multiple Sclerosis / genetics
  • Multiple Sclerosis / therapy*
  • Natalizumab / therapeutic use
  • Recurrence

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Biomarkers
  • Immunoglobulin G
  • Immunoglobulin M
  • Immunologic Factors
  • Natalizumab
  • Interferon-beta

Grants and funding

Roberto Alvarez-Lafuente is recipient of a research contract of the Instituto de Salud Carlos III-Fondo Europeo de Desarrollo Regional (Feder) (CP07/00273). Arias-Leal and Garcia-Martinez are recipients of a technician contract from “REEM: Red Española de Esclerosis Múltiple” (RETICS-REEM RD12/0032/0001; www.reem.es). This work was financially supported by grants from the Instituto de Salud Carlos III-Fondo Europeo de Desarrollo Regional (Feder) (FIS PI12/02349), “Fundación Mutua Madrileña”, and “Fundación LAIR”. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.