title: MHC2TA mRNA levels and human herpesvirus 6 in multiple sclerosis patients treated with interferon beta along two-year follow-up.
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.
authors.affiliation: Servicio de Neurología, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos IdISSC, Madrid, Spain.
authors.forename: Maria Inmaculada
authors.initials: MI
authors.lastname: Dominguez-Mozo
authors.forename: Marta
authors.initials: M
authors.lastname: Garcia-Montojo
authors.forename: Virginia
authors.initials: V
authors.lastname: De Las Heras
authors.forename: Angel
authors.initials: A
authors.lastname: Garcia-Martinez
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Arias-Leal
authors.forename: Ignacio
authors.initials: I
authors.lastname: Casanova
authors.forename: Rafael
authors.initials: R
authors.lastname: Arroyo
authors.forename: Roberto
authors.initials: R
authors.lastname: Alvarez-Lafuente
mesh_terms: D000328:Adult; D057134:Antibodies, Neutralizing; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D015654:Herpesvirus 6, Human / Q000302:isolation & purification*; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D016899:Interferon-beta / Q000276:immunology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000235:genetics / Q000821:virology; D009687:Nuclear Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D019349:Roseolovirus Infections / Q000235:genetics* / Q000276:immunology / Q000821:virology; D015534:Trans-Activators / Q000235:genetics*; D014779:Virus Replication / Q000235:genetics
chemical_list: D057134:Antibodies, Neutralizing; D007155:Immunologic Factors; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D016899:Interferon-beta