Key result
The absence of HHV-6 in serum and an increase in MHC2TA expression were associated with a significantly higher clinical response rate to interferon beta treatment compared to the presence of HHV-6 and decreased MHC2TA expression (58.6% vs 23.8%, p=0.004).
Why the study?
Does interferon beta treatment alter MHC2TA mRNA levels and HHV-6 active infection, and do these markers correlate with clinical response in patients with relapsing-remitting multiple sclerosis?
Cohort (n=154)
Does interferon beta treatment alter MHC2TA mRNA levels and HHV-6 active infection, and do these markers correlate with clinical response in patients with relapsing-remitting multiple sclerosis?
In patients with relapsing-remitting multiple sclerosis, the absence of HHV-6 and an increase in MHC2TA expression may serve as markers of good clinical response to interferon beta treatment.
Answers are grounded in this paper and cite their sources.
May identify interferon beta responders in relapsing-remitting MS; hypothesis-generating and requires prospective validation before guiding therapy.
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.
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Domínguez‐Mozo et al. (2012) conducted a cohort in Relapsing-remitting multiple sclerosis (n=154). Absence of HHV-6 and increased MHC2TA expression vs. Presence of HHV-6 and decreased MHC2TA expression was evaluated on Clinical response to IFN-beta treatment (no EDSS progression and no relapses) (p=0.004). The absence of HHV-6 in serum and an increase in MHC2TA expression were associated with a significantly higher clinical response rate to interferon beta treatment compared to the presence of HHV-6 and decreased MHC2TA expression (58.6% vs 23.8%, p=0.004).
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