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Anti-human herpesvirus 6A/B IgG correlates with relapses and progression in multiple sclerosis.

Ortega-Madueño I, Garcia-Montojo M, Dominguez-Mozo MI, Garcia-Martinez A, Arias-Leal AM, Casanova I, Arroyo R, Alvarez-Lafuente R - PLoS ONE (2014)

Bottom Line: We found that 129/187 (69.0%) MS patients with a decrease of the anti-HHV-6A/B IgG titers after 2-years with DMTs were free of relapses and progression vs. 46/113 (40.7%) of MS patients with an increase of the anti-HHV-6A/B IgG titers (p = 0.0000015); the higher significance was found for natalizumab.The measurement of the anti-HHV-6A/B IgG titers could be a good biomarker of clinical response to the different DMTs.However, further longitudinal studies are needed to validate these results.

View Article: PubMed Central - PubMed

Affiliation: Servicio de Análisis Clínicos. Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain.

ABSTRACT

Objective: To analyze the titers of the IgG and IgM antibodies against human herpesvirus 6A/B (HHV-6A/B) in multiple sclerosis (MS) patients treated with different disease modified therapies (DMTs) along two-years of follow-up.

Methods: We collected 2163 serum samples from 596 MS; for 301 MS patients a 2-years follow-up was performed. Serum samples of 337 healthy controls were also analyzed. Anti-HHV-6A/B IgG and IgM were analyzed by ELISA (Panbio).

Results: We found that 129/187 (69.0%) MS patients with a decrease of the anti-HHV-6A/B IgG titers after 2-years with DMTs were free of relapses and progression vs. 46/113 (40.7%) of MS patients with an increase of the anti-HHV-6A/B IgG titers (p = 0.0000015); the higher significance was found for natalizumab. Furthermore, we found that anti-HHV-6A/B IgG titers reached their highest value two weeks before the relapse (p = 0.0142), while the anti-HHV-6A/B IgM titers reached their highest value one month before the relapse (p = 0.0344).

Conclusion: The measurement of the anti-HHV-6A/B IgG titers could be a good biomarker of clinical response to the different DMTs. The increase of the anti-HHV-6A/B IgG and IgM titers predicts the upcoming clinical relapses. However, further longitudinal studies are needed to validate these results.

No MeSH data available.


Related in: MedlinePlus

Percentage of MS patients free of relapses and progression after two years of follow-up from the 301 MS patients included in the longitudinal study.A. DMTs. B. interferon-beta (IFN-beta). C. IFN-beta (only in those MS patients that did not develop NAbs). D. glatiramer acetate (GA). E. natalizumab (NTZ). Four comparisons have been performed for each treatment: MS patients with increased anti-HHV-6A/B IgG titers vs. MS patients with decreased anti-HHV-6A/B IgG titers; MS patients with an increase of the anti-HHV-6A/B IgG titers >5% vs. MS patients with a decrease of the anti-HHV-6A/B IgG titers >5%; MS patients with an increase or decrease of the anti-HHV-6A/B IgG titers >10%; MS patients with an increase or decrease of the anti-HHV-6A/B IgG titers >20%.
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pone-0104836-g001: Percentage of MS patients free of relapses and progression after two years of follow-up from the 301 MS patients included in the longitudinal study.A. DMTs. B. interferon-beta (IFN-beta). C. IFN-beta (only in those MS patients that did not develop NAbs). D. glatiramer acetate (GA). E. natalizumab (NTZ). Four comparisons have been performed for each treatment: MS patients with increased anti-HHV-6A/B IgG titers vs. MS patients with decreased anti-HHV-6A/B IgG titers; MS patients with an increase of the anti-HHV-6A/B IgG titers >5% vs. MS patients with a decrease of the anti-HHV-6A/B IgG titers >5%; MS patients with an increase or decrease of the anti-HHV-6A/B IgG titers >10%; MS patients with an increase or decrease of the anti-HHV-6A/B IgG titers >20%.

Mentions: As can be seen in Figures 1A–1E, we found a correlation between the variation of the anti-HHV-6A/B IgG titers and the clinical response (absence of relapses and progression after two-years of follow-up) in MS patients treated with the different DMTs: 129/187 (69.0%) MS patients with a decrease of the anti-HHV-6A/B IgG titers were free of relapses and progression vs. 46/113 (40.7%) of MS patients with an increase of the anti-HHV-6A/B IgG titers (p = 0.0000015); statistical significant differences were found for each one of the DMTs, although the higher significance was found for natalizumab: 45/58 (77.6%) vs. 7/23 (30.4%) (p = 0.00007; O.R. = 7.9), respectively. The percentage of clinical responders was greater among those MS patients with greater reductions of the anti-HHV-6A/B IgG titers, while the percentage of clinical responders in MS patients with an increase in their anti-HHV-6A/B IgG titers was lower when the percentage of increase was greater (Figures 1A–1E).


Anti-human herpesvirus 6A/B IgG correlates with relapses and progression in multiple sclerosis.

Ortega-Madueño I, Garcia-Montojo M, Dominguez-Mozo MI, Garcia-Martinez A, Arias-Leal AM, Casanova I, Arroyo R, Alvarez-Lafuente R - PLoS ONE (2014)

Percentage of MS patients free of relapses and progression after two years of follow-up from the 301 MS patients included in the longitudinal study.A. DMTs. B. interferon-beta (IFN-beta). C. IFN-beta (only in those MS patients that did not develop NAbs). D. glatiramer acetate (GA). E. natalizumab (NTZ). Four comparisons have been performed for each treatment: MS patients with increased anti-HHV-6A/B IgG titers vs. MS patients with decreased anti-HHV-6A/B IgG titers; MS patients with an increase of the anti-HHV-6A/B IgG titers >5% vs. MS patients with a decrease of the anti-HHV-6A/B IgG titers >5%; MS patients with an increase or decrease of the anti-HHV-6A/B IgG titers >10%; MS patients with an increase or decrease of the anti-HHV-6A/B IgG titers >20%.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4128748&req=5

pone-0104836-g001: Percentage of MS patients free of relapses and progression after two years of follow-up from the 301 MS patients included in the longitudinal study.A. DMTs. B. interferon-beta (IFN-beta). C. IFN-beta (only in those MS patients that did not develop NAbs). D. glatiramer acetate (GA). E. natalizumab (NTZ). Four comparisons have been performed for each treatment: MS patients with increased anti-HHV-6A/B IgG titers vs. MS patients with decreased anti-HHV-6A/B IgG titers; MS patients with an increase of the anti-HHV-6A/B IgG titers >5% vs. MS patients with a decrease of the anti-HHV-6A/B IgG titers >5%; MS patients with an increase or decrease of the anti-HHV-6A/B IgG titers >10%; MS patients with an increase or decrease of the anti-HHV-6A/B IgG titers >20%.
Mentions: As can be seen in Figures 1A–1E, we found a correlation between the variation of the anti-HHV-6A/B IgG titers and the clinical response (absence of relapses and progression after two-years of follow-up) in MS patients treated with the different DMTs: 129/187 (69.0%) MS patients with a decrease of the anti-HHV-6A/B IgG titers were free of relapses and progression vs. 46/113 (40.7%) of MS patients with an increase of the anti-HHV-6A/B IgG titers (p = 0.0000015); statistical significant differences were found for each one of the DMTs, although the higher significance was found for natalizumab: 45/58 (77.6%) vs. 7/23 (30.4%) (p = 0.00007; O.R. = 7.9), respectively. The percentage of clinical responders was greater among those MS patients with greater reductions of the anti-HHV-6A/B IgG titers, while the percentage of clinical responders in MS patients with an increase in their anti-HHV-6A/B IgG titers was lower when the percentage of increase was greater (Figures 1A–1E).

Bottom Line: We found that 129/187 (69.0%) MS patients with a decrease of the anti-HHV-6A/B IgG titers after 2-years with DMTs were free of relapses and progression vs. 46/113 (40.7%) of MS patients with an increase of the anti-HHV-6A/B IgG titers (p = 0.0000015); the higher significance was found for natalizumab.The measurement of the anti-HHV-6A/B IgG titers could be a good biomarker of clinical response to the different DMTs.However, further longitudinal studies are needed to validate these results.

View Article: PubMed Central - PubMed

Affiliation: Servicio de Análisis Clínicos. Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain.

ABSTRACT

Objective: To analyze the titers of the IgG and IgM antibodies against human herpesvirus 6A/B (HHV-6A/B) in multiple sclerosis (MS) patients treated with different disease modified therapies (DMTs) along two-years of follow-up.

Methods: We collected 2163 serum samples from 596 MS; for 301 MS patients a 2-years follow-up was performed. Serum samples of 337 healthy controls were also analyzed. Anti-HHV-6A/B IgG and IgM were analyzed by ELISA (Panbio).

Results: We found that 129/187 (69.0%) MS patients with a decrease of the anti-HHV-6A/B IgG titers after 2-years with DMTs were free of relapses and progression vs. 46/113 (40.7%) of MS patients with an increase of the anti-HHV-6A/B IgG titers (p = 0.0000015); the higher significance was found for natalizumab. Furthermore, we found that anti-HHV-6A/B IgG titers reached their highest value two weeks before the relapse (p = 0.0142), while the anti-HHV-6A/B IgM titers reached their highest value one month before the relapse (p = 0.0344).

Conclusion: The measurement of the anti-HHV-6A/B IgG titers could be a good biomarker of clinical response to the different DMTs. The increase of the anti-HHV-6A/B IgG and IgM titers predicts the upcoming clinical relapses. However, further longitudinal studies are needed to validate these results.

No MeSH data available.


Related in: MedlinePlus