Humoral responses to herpesviruses are associated with neurodegeneration after a demyelinating event: Results from the Multi-Center SET study

Robert Zivadinov, Jamie Chin, Dana Horakova, Niels Bergsland, Bianca Weinstock-Guttman, Miriam Tamaño-Blanco, Darlene Badgett, Jesper Hagemeier, Michaela Tyblova, Ellen Carl, Jan Krasensky, Manuela Vaneckova, Zdenek Seidl, Michael G. Dwyer, Eva Havrdova, Murali Ramanathan

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Objectives: To investigate the associations between antibody responses to herpesviruses and the development of thalamic, total deep gray matter, cortical and central atrophy in high-risk clinically isolated syndromes (CIS) after the first demyelinating event. Methods: We analyzed volumetric brain outcomes in 193 CIS patients enrolled in a multi-center study of high-risk CIS. All patients had 2 or more MRI brain lesions and two or more oligoclonal bands in cerebrospinal fluid. Serum samples obtained at the screening visit prior to any treatment were analyzed for IgG antibodies against cytomegalovirus (anti-CMV) and Epstein-Barr virus (EBV) viral capsid antigen (VCA). All patients were treated with interferon-beta. Clinical and MRI assessments were obtained at baseline, 6, 12, and 24. months. Results: Anti-EBV VCA highest quartile status was associated with regional atrophy measures for percent decrease in thalamus. Anti-CMV positivity was associated with greater total deep gray matter atrophy and whole brain atrophy. Anti-EBV VCA highest quartile status was associated as trends with greater whole brain, gray matter atrophy and central atrophy. The associations of anti-EBV VCA antibodies with thalamic atrophy were mediated by its associations with T2 lesions whereas the associations of anti-CMV positivity with deep gray matter atrophy were relatively independent of T2 lesions. Conclusions: Antibody responses to EBV and CMV are associated with global and regional brain atrophy in CIS patients treated with interferon-beta.

Original languageEnglish
Pages (from-to)58-64
Number of pages7
JournalJournal of Neuroimmunology
Volume273
Issue number1-2
DOIs
Publication statusPublished - 2014

Fingerprint

Herpesviridae
Atrophy
Human Herpesvirus 4
Brain
Interferon-beta
Cytomegalovirus
Antibody Formation
Antibodies
Oligoclonal Bands
Thalamus
Cerebrospinal Fluid
Immunoglobulin G
Gray Matter
Epstein-Barr viral capsid antigen

Keywords

  • Cytomegalovirus
  • Deep gray matter atrophy
  • Environmental factors
  • Epstein-Barr virus

ASJC Scopus subject areas

  • Immunology
  • Clinical Neurology
  • Immunology and Allergy
  • Neurology

Cite this

Humoral responses to herpesviruses are associated with neurodegeneration after a demyelinating event : Results from the Multi-Center SET study. / Zivadinov, Robert; Chin, Jamie; Horakova, Dana; Bergsland, Niels; Weinstock-Guttman, Bianca; Tamaño-Blanco, Miriam; Badgett, Darlene; Hagemeier, Jesper; Tyblova, Michaela; Carl, Ellen; Krasensky, Jan; Vaneckova, Manuela; Seidl, Zdenek; Dwyer, Michael G.; Havrdova, Eva; Ramanathan, Murali.

In: Journal of Neuroimmunology, Vol. 273, No. 1-2, 2014, p. 58-64.

Research output: Contribution to journalArticle

Zivadinov, R, Chin, J, Horakova, D, Bergsland, N, Weinstock-Guttman, B, Tamaño-Blanco, M, Badgett, D, Hagemeier, J, Tyblova, M, Carl, E, Krasensky, J, Vaneckova, M, Seidl, Z, Dwyer, MG, Havrdova, E & Ramanathan, M 2014, 'Humoral responses to herpesviruses are associated with neurodegeneration after a demyelinating event: Results from the Multi-Center SET study', Journal of Neuroimmunology, vol. 273, no. 1-2, pp. 58-64. https://doi.org/10.1016/j.jneuroim.2014.04.012
Zivadinov, Robert ; Chin, Jamie ; Horakova, Dana ; Bergsland, Niels ; Weinstock-Guttman, Bianca ; Tamaño-Blanco, Miriam ; Badgett, Darlene ; Hagemeier, Jesper ; Tyblova, Michaela ; Carl, Ellen ; Krasensky, Jan ; Vaneckova, Manuela ; Seidl, Zdenek ; Dwyer, Michael G. ; Havrdova, Eva ; Ramanathan, Murali. / Humoral responses to herpesviruses are associated with neurodegeneration after a demyelinating event : Results from the Multi-Center SET study. In: Journal of Neuroimmunology. 2014 ; Vol. 273, No. 1-2. pp. 58-64.
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abstract = "Objectives: To investigate the associations between antibody responses to herpesviruses and the development of thalamic, total deep gray matter, cortical and central atrophy in high-risk clinically isolated syndromes (CIS) after the first demyelinating event. Methods: We analyzed volumetric brain outcomes in 193 CIS patients enrolled in a multi-center study of high-risk CIS. All patients had 2 or more MRI brain lesions and two or more oligoclonal bands in cerebrospinal fluid. Serum samples obtained at the screening visit prior to any treatment were analyzed for IgG antibodies against cytomegalovirus (anti-CMV) and Epstein-Barr virus (EBV) viral capsid antigen (VCA). All patients were treated with interferon-beta. Clinical and MRI assessments were obtained at baseline, 6, 12, and 24. months. Results: Anti-EBV VCA highest quartile status was associated with regional atrophy measures for percent decrease in thalamus. Anti-CMV positivity was associated with greater total deep gray matter atrophy and whole brain atrophy. Anti-EBV VCA highest quartile status was associated as trends with greater whole brain, gray matter atrophy and central atrophy. The associations of anti-EBV VCA antibodies with thalamic atrophy were mediated by its associations with T2 lesions whereas the associations of anti-CMV positivity with deep gray matter atrophy were relatively independent of T2 lesions. Conclusions: Antibody responses to EBV and CMV are associated with global and regional brain atrophy in CIS patients treated with interferon-beta.",
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T1 - Humoral responses to herpesviruses are associated with neurodegeneration after a demyelinating event

T2 - Results from the Multi-Center SET study

AU - Zivadinov, Robert

AU - Chin, Jamie

AU - Horakova, Dana

AU - Bergsland, Niels

AU - Weinstock-Guttman, Bianca

AU - Tamaño-Blanco, Miriam

AU - Badgett, Darlene

AU - Hagemeier, Jesper

AU - Tyblova, Michaela

AU - Carl, Ellen

AU - Krasensky, Jan

AU - Vaneckova, Manuela

AU - Seidl, Zdenek

AU - Dwyer, Michael G.

AU - Havrdova, Eva

AU - Ramanathan, Murali

PY - 2014

Y1 - 2014

N2 - Objectives: To investigate the associations between antibody responses to herpesviruses and the development of thalamic, total deep gray matter, cortical and central atrophy in high-risk clinically isolated syndromes (CIS) after the first demyelinating event. Methods: We analyzed volumetric brain outcomes in 193 CIS patients enrolled in a multi-center study of high-risk CIS. All patients had 2 or more MRI brain lesions and two or more oligoclonal bands in cerebrospinal fluid. Serum samples obtained at the screening visit prior to any treatment were analyzed for IgG antibodies against cytomegalovirus (anti-CMV) and Epstein-Barr virus (EBV) viral capsid antigen (VCA). All patients were treated with interferon-beta. Clinical and MRI assessments were obtained at baseline, 6, 12, and 24. months. Results: Anti-EBV VCA highest quartile status was associated with regional atrophy measures for percent decrease in thalamus. Anti-CMV positivity was associated with greater total deep gray matter atrophy and whole brain atrophy. Anti-EBV VCA highest quartile status was associated as trends with greater whole brain, gray matter atrophy and central atrophy. The associations of anti-EBV VCA antibodies with thalamic atrophy were mediated by its associations with T2 lesions whereas the associations of anti-CMV positivity with deep gray matter atrophy were relatively independent of T2 lesions. Conclusions: Antibody responses to EBV and CMV are associated with global and regional brain atrophy in CIS patients treated with interferon-beta.

AB - Objectives: To investigate the associations between antibody responses to herpesviruses and the development of thalamic, total deep gray matter, cortical and central atrophy in high-risk clinically isolated syndromes (CIS) after the first demyelinating event. Methods: We analyzed volumetric brain outcomes in 193 CIS patients enrolled in a multi-center study of high-risk CIS. All patients had 2 or more MRI brain lesions and two or more oligoclonal bands in cerebrospinal fluid. Serum samples obtained at the screening visit prior to any treatment were analyzed for IgG antibodies against cytomegalovirus (anti-CMV) and Epstein-Barr virus (EBV) viral capsid antigen (VCA). All patients were treated with interferon-beta. Clinical and MRI assessments were obtained at baseline, 6, 12, and 24. months. Results: Anti-EBV VCA highest quartile status was associated with regional atrophy measures for percent decrease in thalamus. Anti-CMV positivity was associated with greater total deep gray matter atrophy and whole brain atrophy. Anti-EBV VCA highest quartile status was associated as trends with greater whole brain, gray matter atrophy and central atrophy. The associations of anti-EBV VCA antibodies with thalamic atrophy were mediated by its associations with T2 lesions whereas the associations of anti-CMV positivity with deep gray matter atrophy were relatively independent of T2 lesions. Conclusions: Antibody responses to EBV and CMV are associated with global and regional brain atrophy in CIS patients treated with interferon-beta.

KW - Cytomegalovirus

KW - Deep gray matter atrophy

KW - Environmental factors

KW - Epstein-Barr virus

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