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

Dominguez-Mozo MI, Garcia-Montojo M, De Las Heras V, Garcia-Martinez A, Arias-Leal AM, Casanova I, Arroyo R, Alvarez-Lafuente R - BMC Neurol (2012)

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Servicio de Neurología, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos IdISSC, Madrid, Spain.

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.

Show MeSH

Related in: MedlinePlus

MHC2TA expression levels as NR. A. Mean NR at each visit. B. MS patients with minor allele C vs. MS patients without minor allele C. C. MS patients with minor allele C and HHV-6 in serum at basal visit vs. MS patients without minor allele C and without HHV-6 active infection at basal visit.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3585729&req=5

Figure 1: MHC2TA expression levels as NR. A. Mean NR at each visit. B. MS patients with minor allele C vs. MS patients without minor allele C. C. MS patients with minor allele C and HHV-6 in serum at basal visit vs. MS patients without minor allele C and without HHV-6 active infection at basal visit.

Mentions: When we analyzed the influence of IFN-beta treatment on the expression of MHC2TA gene in the whole MS population, we did not find any statistical significant difference between the basal visit and the 24-month visit (p = 0.134): mean NR was 1.4 at basal visit, 1.3 after six months of treatment, 1.5 twelve months later, 1.8 at the 18-month visit, and 2.1 two years later after starting IFN-beta treatment (Figure 1A). No statistical significant differences were found between MS patients with and without NAbs.


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

Dominguez-Mozo MI, Garcia-Montojo M, De Las Heras V, Garcia-Martinez A, Arias-Leal AM, Casanova I, Arroyo R, Alvarez-Lafuente R - BMC Neurol (2012)

MHC2TA expression levels as NR. A. Mean NR at each visit. B. MS patients with minor allele C vs. MS patients without minor allele C. C. MS patients with minor allele C and HHV-6 in serum at basal visit vs. MS patients without minor allele C and without HHV-6 active infection at basal visit.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3585729&req=5

Figure 1: MHC2TA expression levels as NR. A. Mean NR at each visit. B. MS patients with minor allele C vs. MS patients without minor allele C. C. MS patients with minor allele C and HHV-6 in serum at basal visit vs. MS patients without minor allele C and without HHV-6 active infection at basal visit.
Mentions: When we analyzed the influence of IFN-beta treatment on the expression of MHC2TA gene in the whole MS population, we did not find any statistical significant difference between the basal visit and the 24-month visit (p = 0.134): mean NR was 1.4 at basal visit, 1.3 after six months of treatment, 1.5 twelve months later, 1.8 at the 18-month visit, and 2.1 two years later after starting IFN-beta treatment (Figure 1A). No statistical significant differences were found between MS patients with and without NAbs.

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Servicio de Neurología, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos IdISSC, Madrid, Spain.

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.

Show MeSH
Related in: MedlinePlus