Positivity of cytomegalovirus antibodies predicts a better clinical and radiological outcome in multiple sclerosis patients

Robert Zivadinov, Davide Nasuelli, Maria Antonietta Tommasi, Maurizia Serafin, Alessio Bratina, Maja Ukmar, Istvan Pirko, Aaron J. Johnson, Christina Furlan, Roberto S. Pozzi-Mucelli, Luisa Monti-Bragadin, Attilio Grop, Massimo Zambon, Rodolfo M. Antonello, Giuseppe Cazzato, Marino Zorzon

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Objectives: To establish the relationship between the presence and titer of virus-specific serum- and cerebrospinal fluid (CSF)-antibodies in multiple sclerosis (MS) patients and disease severity measured with different quantitative magnetic resonance imaging (MRI) techniques. Methods: We investigated an association between clinical ana MRI measures of disease activity and the presence and titer of IgG antibodies against seven common viruses (measles, rubella, herpes simplex virus type 1 and 2, varicella zoster virus, cytomegalovirus (CMV) and Epstein-Barr virus). One hundred and forty (90 female/50 male) patients with definite MS and 131 age and sex-matched controls participated in the study. Antibody positivity and titer were ascertained by the enzyme linked immunosorbent assay (ELISA) technique and clinical assessment was performed by evaluating the expanded disability status scale (EDSS) score and the lifetime relapse rate (LRR). T1- and T2-lesion loads (LL) and the brain parenchymal fraction (BPF) were calculated. Results: Multiple analyses showed that there was an association between antibody positivity against CMV and higher titer and better clinical and MRI outcomes. The cluster analyses indicated that patients positive for antibodies against CMV had significantly older age at onset (uncorr p=0.007 and corr p=0.009), lower LRR (uncorr p=0.003 and corr p=0.03) and higher BPF (uncorr p=0.004 and pcorr p=0.04). CMV-positive patients who had higher antibody titer showed lower T2-LL (uncorr p=0.003 and corr p=0.03) and higher BPF (uncorr p=0.006 and corr p=0.05). Discussion: Surprisingly, our results focused attention on the 'protective' role of a particular virus. CMV is probably capable of triggering some immunomodulating/immune evasion mechanisms which may decrease immune reactivity in MS patients. Further studies are needed to confirm and elucidate our study results on a larger sample of MS patients and in animal model studies.

Original languageEnglish (US)
Pages (from-to)262-269
Number of pages8
JournalNeurological Research
Volume28
Issue number3
DOIs
StatePublished - Apr 2006
Externally publishedYes

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Cytomegalovirus
Multiple Sclerosis
Antibodies
Magnetic Resonance Imaging
Brain
Immunosorbent Techniques
Rubella virus
Immune Evasion
Recurrence
Measles virus
Human Herpesvirus 3
Human Herpesvirus 2
Human Herpesvirus 1
Viral Load
Human Herpesvirus 4
Age of Onset
Cluster Analysis
Cerebrospinal Fluid
Animal Models
Immunoglobulin G

Keywords

  • Cytomegalovirus
  • Disease severity
  • Immune evasion
  • Immunomodulation
  • MRI
  • Multiple sclerosis

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

Cite this

Zivadinov, R., Nasuelli, D., Tommasi, M. A., Serafin, M., Bratina, A., Ukmar, M., ... Zorzon, M. (2006). Positivity of cytomegalovirus antibodies predicts a better clinical and radiological outcome in multiple sclerosis patients. Neurological Research, 28(3), 262-269. https://doi.org/10.1179/016164106X98134

Positivity of cytomegalovirus antibodies predicts a better clinical and radiological outcome in multiple sclerosis patients. / Zivadinov, Robert; Nasuelli, Davide; Tommasi, Maria Antonietta; Serafin, Maurizia; Bratina, Alessio; Ukmar, Maja; Pirko, Istvan; Johnson, Aaron J.; Furlan, Christina; Pozzi-Mucelli, Roberto S.; Monti-Bragadin, Luisa; Grop, Attilio; Zambon, Massimo; Antonello, Rodolfo M.; Cazzato, Giuseppe; Zorzon, Marino.

In: Neurological Research, Vol. 28, No. 3, 04.2006, p. 262-269.

Research output: Contribution to journalArticle

Zivadinov, R, Nasuelli, D, Tommasi, MA, Serafin, M, Bratina, A, Ukmar, M, Pirko, I, Johnson, AJ, Furlan, C, Pozzi-Mucelli, RS, Monti-Bragadin, L, Grop, A, Zambon, M, Antonello, RM, Cazzato, G & Zorzon, M 2006, 'Positivity of cytomegalovirus antibodies predicts a better clinical and radiological outcome in multiple sclerosis patients', Neurological Research, vol. 28, no. 3, pp. 262-269. https://doi.org/10.1179/016164106X98134
Zivadinov, Robert ; Nasuelli, Davide ; Tommasi, Maria Antonietta ; Serafin, Maurizia ; Bratina, Alessio ; Ukmar, Maja ; Pirko, Istvan ; Johnson, Aaron J. ; Furlan, Christina ; Pozzi-Mucelli, Roberto S. ; Monti-Bragadin, Luisa ; Grop, Attilio ; Zambon, Massimo ; Antonello, Rodolfo M. ; Cazzato, Giuseppe ; Zorzon, Marino. / Positivity of cytomegalovirus antibodies predicts a better clinical and radiological outcome in multiple sclerosis patients. In: Neurological Research. 2006 ; Vol. 28, No. 3. pp. 262-269.
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abstract = "Objectives: To establish the relationship between the presence and titer of virus-specific serum- and cerebrospinal fluid (CSF)-antibodies in multiple sclerosis (MS) patients and disease severity measured with different quantitative magnetic resonance imaging (MRI) techniques. Methods: We investigated an association between clinical ana MRI measures of disease activity and the presence and titer of IgG antibodies against seven common viruses (measles, rubella, herpes simplex virus type 1 and 2, varicella zoster virus, cytomegalovirus (CMV) and Epstein-Barr virus). One hundred and forty (90 female/50 male) patients with definite MS and 131 age and sex-matched controls participated in the study. Antibody positivity and titer were ascertained by the enzyme linked immunosorbent assay (ELISA) technique and clinical assessment was performed by evaluating the expanded disability status scale (EDSS) score and the lifetime relapse rate (LRR). T1- and T2-lesion loads (LL) and the brain parenchymal fraction (BPF) were calculated. Results: Multiple analyses showed that there was an association between antibody positivity against CMV and higher titer and better clinical and MRI outcomes. The cluster analyses indicated that patients positive for antibodies against CMV had significantly older age at onset (uncorr p=0.007 and corr p=0.009), lower LRR (uncorr p=0.003 and corr p=0.03) and higher BPF (uncorr p=0.004 and pcorr p=0.04). CMV-positive patients who had higher antibody titer showed lower T2-LL (uncorr p=0.003 and corr p=0.03) and higher BPF (uncorr p=0.006 and corr p=0.05). Discussion: Surprisingly, our results focused attention on the 'protective' role of a particular virus. CMV is probably capable of triggering some immunomodulating/immune evasion mechanisms which may decrease immune reactivity in MS patients. Further studies are needed to confirm and elucidate our study results on a larger sample of MS patients and in animal model studies.",
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AU - Zivadinov, Robert

AU - Nasuelli, Davide

AU - Tommasi, Maria Antonietta

AU - Serafin, Maurizia

AU - Bratina, Alessio

AU - Ukmar, Maja

AU - Pirko, Istvan

AU - Johnson, Aaron J.

AU - Furlan, Christina

AU - Pozzi-Mucelli, Roberto S.

AU - Monti-Bragadin, Luisa

AU - Grop, Attilio

AU - Zambon, Massimo

AU - Antonello, Rodolfo M.

AU - Cazzato, Giuseppe

AU - Zorzon, Marino

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N2 - Objectives: To establish the relationship between the presence and titer of virus-specific serum- and cerebrospinal fluid (CSF)-antibodies in multiple sclerosis (MS) patients and disease severity measured with different quantitative magnetic resonance imaging (MRI) techniques. Methods: We investigated an association between clinical ana MRI measures of disease activity and the presence and titer of IgG antibodies against seven common viruses (measles, rubella, herpes simplex virus type 1 and 2, varicella zoster virus, cytomegalovirus (CMV) and Epstein-Barr virus). One hundred and forty (90 female/50 male) patients with definite MS and 131 age and sex-matched controls participated in the study. Antibody positivity and titer were ascertained by the enzyme linked immunosorbent assay (ELISA) technique and clinical assessment was performed by evaluating the expanded disability status scale (EDSS) score and the lifetime relapse rate (LRR). T1- and T2-lesion loads (LL) and the brain parenchymal fraction (BPF) were calculated. Results: Multiple analyses showed that there was an association between antibody positivity against CMV and higher titer and better clinical and MRI outcomes. The cluster analyses indicated that patients positive for antibodies against CMV had significantly older age at onset (uncorr p=0.007 and corr p=0.009), lower LRR (uncorr p=0.003 and corr p=0.03) and higher BPF (uncorr p=0.004 and pcorr p=0.04). CMV-positive patients who had higher antibody titer showed lower T2-LL (uncorr p=0.003 and corr p=0.03) and higher BPF (uncorr p=0.006 and corr p=0.05). Discussion: Surprisingly, our results focused attention on the 'protective' role of a particular virus. CMV is probably capable of triggering some immunomodulating/immune evasion mechanisms which may decrease immune reactivity in MS patients. Further studies are needed to confirm and elucidate our study results on a larger sample of MS patients and in animal model studies.

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