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

Maria Inmaculada Dominguez-Mozo,Angel Garcia-Martinez,Marta Garcia-Montojo,Virginia De Las Heras,Ignacio Casanova,Roberto Alvarez-Lafuente,Rafael Arroyo,Ana Maria Arias-Leal

doi:10.1186/1471-2377-12-107

Abstract

BackgroundIn 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.MethodsBlood 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.ResultsWe 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.ConclusionsMHC2TA 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.

Highlights

In previous studies we found that MHC2TA +1614 genotype frequency was very different when multiple sclerosis (MS) patients with and without human herpesvirus 6 (HHV-6) in serum samples were compared; a different clinical behavior was described
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
In a subsequent study [2], we verified the previous association that we had found between the HHV-6 active replication and the presence of MHC2TA rs4774C; we found that those MS patients with minor allele C and HHV-6 active infection had different clinical behavior since they were worse clinical responders to IFN-beta treatment, and they had a higher progression in the first two years of the disease

Summary

Introduction

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 described. In a previous study in the Spanish multiple sclerosis (MS) population, our group found that the MHC2TA +1614 genotype frequency was very different when MS patients with human herpesvirus 6 (HHV-6) were compared with MS patients without this virus [1]. In a subsequent study [2], we verified the previous association that we had found between the HHV-6 active replication and the presence of MHC2TA rs4774C; we found that those MS patients with minor allele C and HHV-6 active infection had different clinical behavior since they were worse clinical responders to IFN-beta treatment, and they had a higher progression in the first two years of the disease.

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