MHC2TA mRNA levels and human herpesvirus 6 in multiple sclerosis patients treated with interferon beta along two-year follow-up

BMC Neurol. 2012 Sep 25:12:107. doi: 10.1186/1471-2377-12-107.

Abstract

Background: In previous studies we found that MHC2TA +1614 genotype frequency was very different when MS patients with and without human herpesvirus 6 (HHV-6) in serum samples were compared; a different clinical behavior was also described. The purpose of the study was: 1. To evaluate if MHC2TA expression in MS patients was influenced by interferon beta (IFN-beta) treatment. 2. To study MHC2TA expression in MS patients with and without minor allele C. 3. To analyze the relation between MHC2TA mRNA levels and HHV-6 active infection in MS patients.

Methods: Blood and serum samples of 154 MS patients were collected in five programmed visits: basal (prior to beginning IFN-beta treatment), six, twelve, eighteen and twenty-four months later. HHV-6 in serum and MHC2TA mRNA levels were evaluated by PCR and RT-PCR, respectively. Neutralizing antibodies (NAbs) against IFN-beta were analyzed by the cytopathic effect assay.

Results: We found that MHC2TA mRNA levels were significantly lower among MS patients with HHV-6 active infection at the basal visit (without treatment) than in those MS patients without HHV-6 active infection at the basal visit (p = 0.012); in all the positive samples we only found variant A. Furthermore, 58/99 (58.6%) MS patients without HHV-6 along the five programmed visits and an increase of MHC2TA expression after two-years of IFN-beta treatment were clinical responders vs. 5/21 (23.8%) among those MS patients with HHV-6 and a decrease of MHC2TA mRNA levels along the two-years with IFN-beta treatment (p = 0.004); no differences were found between patients with and without NAbs.

Conclusions: MHC2TA mRNA levels could be decreased by the active replication of HHV-6; the absence of HHV-6 in serum and the increase of MHC2TA expression could be further studied as markers of good clinical response to IFN-beta treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Neutralizing
  • Female
  • Gene Frequency
  • Genotype
  • Herpesvirus 6, Human / isolation & purification*
  • Humans
  • Immunologic Factors / therapeutic use*
  • Interferon-beta / immunology
  • Interferon-beta / therapeutic use*
  • Male
  • Middle Aged
  • Multiple Sclerosis / drug therapy*
  • Multiple Sclerosis / genetics
  • Multiple Sclerosis / virology
  • Nuclear Proteins / genetics*
  • RNA, Messenger / genetics
  • Roseolovirus Infections / genetics*
  • Roseolovirus Infections / immunology
  • Roseolovirus Infections / virology
  • Trans-Activators / genetics*
  • Virus Replication / genetics

Substances

  • Antibodies, Neutralizing
  • Immunologic Factors
  • MHC class II transactivator protein
  • Nuclear Proteins
  • RNA, Messenger
  • Trans-Activators
  • Interferon-beta