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

• Published in: BMC neurology 2012-09, Vol.12 (1), p.107-107, Article 107
• Main Authors: Dominguez-Mozo, Maria Inmaculada, Garcia-Montojo, Marta, De Las Heras, Virginia, Garcia-Martinez, Angel, Arias-Leal, Ana Maria, Casanova, Ignacio, Arroyo, Rafael, Alvarez-Lafuente, Roberto
• Format: Article
• Language: English
• Subjects: Adult; Antibodies, Neutralizing; Biological response modifiers; Care and treatment; Comparative analysis; Deoxyribonucleic acid; DNA; Dosage and administration; Female; Gene Frequency; Genetic aspects; Genotype; Health aspects; Herpes; Herpesvirus 6, Human - isolation & purification; Herpesvirus diseases; HHV-6; Human herpesvirus 6; Humans; Immunologic Factors - therapeutic use; Infection; Infections; Interferon beta; Interferon-beta - immunology; Interferon-beta - therapeutic use; Major histocompatibility complex; Male; Medical research; Medicine, Experimental; Messenger RNA; MHC2TA; Middle Aged; Multiple sclerosis; Multiple Sclerosis - drug therapy; Multiple Sclerosis - genetics; Multiple Sclerosis - virology; Nuclear Proteins - genetics; Physiological aspects; Quantitative RT-PCR; RNA, Messenger - genetics; Roseolovirus Infections - genetics; Roseolovirus Infections - immunology; Roseolovirus Infections - virology; Studies; Trans-Activators - genetics; Virus Replication - genetics
• ISSN: 1471-2377; 1471-2377
• DOI: 10.1186/1471-2377-12-107

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. 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. 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. 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.