Gene-environment interactions between HLA B7/A2, EBV antibodies are associated with MRI injury in multiple sclerosis

Robert Zivadinov, Bianca Weinstock-Guttman, Marino Zorzon, Laura Uxa, Maurizia Serafin, Antonio Bosco, Alessio Bratina, Cosimo Maggiore, Attilio Grop, Maria Antonietta Tommasi, Bhooma Srinivasaraghavan, Murali Ramanathan

Research output: Contribution to journalArticle

Abstract

Purpose: To determine the role of gene-environmental interactions between the Class I and Class II HLA alleles and the humoral anti-Epstein-Barr Virus (EBV) responses in the development of brain injury and clinical disability in multiple sclerosis (MS) patients. Methods: A total of 93 MS patients (62 females; 31 males) and 122 healthy controls underwent HLA typing and testing for antibodies against EBV. The MS patients underwent brain MRI and quantitative measurements of T1- and T2-lesion volumes (LVs) and brain parenchymal fraction (BPF) were obtained. There were 54 MS cases that underwent MRI and EBV-antibody assessments at the 3-year follow-up. The anti-EBV panel included measurements of the levels of anti-EBV early antigen (EA) IgG, anti-EBV nuclear antigen (EBNA) IgG and anti-EBV viral capsid antigen (VCA) IgM and anti-EBV VCA IgG. The relationships between HLA alleles, anti-EBV antibody levels, MRI and clinical parameters were assessed in regression analysis. Results: The presence of HLA B7 was associated with increased T1-LV and trends indicating increased anti-EBV VCA IgG levels, higher disability (EDSS) and more destructive MRI parameters (increased T2-LV and decreased BPF). The presence of HLA A2 was associated with lower EDSS and a trend toward decreased anti-EBV VCA IgG levels; the associations with MRI variables were not significant. The HLA B7-A2 haplotype was significantly associated with higher T2-LV and T1-LV and a trend toward lower BPF was observed. Conclusions: Our data suggest that gene-environment interactions between specific HLA Class I loci and EBV exposure are associated with MRI markers of lesion injury and brain atrophy in MS patients.

Original languageEnglish
Pages (from-to)123-130
Number of pages8
JournalJournal of Neuroimmunology
Volume209
Issue number1-2
DOIs
Publication statusPublished - Apr 30 2009

Fingerprint

HLA-B7 Antigen
HLA-A2 Antigen
Gene-Environment Interaction
Human Herpesvirus 4
Multiple Sclerosis
Antibodies
Wounds and Injuries
Immunoglobulin G
Brain
Brain Injuries
Alleles
Epstein-Barr Virus Nuclear Antigens
Histocompatibility Testing
Haplotypes
Atrophy

Keywords

  • Epstein-Barr virus
  • Gene-environment interactions
  • HLA
  • MHC
  • Multiple sclerosis

ASJC Scopus subject areas

  • Immunology
  • Clinical Neurology
  • Immunology and Allergy
  • Neurology

Cite this

Zivadinov, R., Weinstock-Guttman, B., Zorzon, M., Uxa, L., Serafin, M., Bosco, A., ... Ramanathan, M. (2009). Gene-environment interactions between HLA B7/A2, EBV antibodies are associated with MRI injury in multiple sclerosis. Journal of Neuroimmunology, 209(1-2), 123-130. https://doi.org/10.1016/j.jneuroim.2009.01.023

Gene-environment interactions between HLA B7/A2, EBV antibodies are associated with MRI injury in multiple sclerosis. / Zivadinov, Robert; Weinstock-Guttman, Bianca; Zorzon, Marino; Uxa, Laura; Serafin, Maurizia; Bosco, Antonio; Bratina, Alessio; Maggiore, Cosimo; Grop, Attilio; Tommasi, Maria Antonietta; Srinivasaraghavan, Bhooma; Ramanathan, Murali.

In: Journal of Neuroimmunology, Vol. 209, No. 1-2, 30.04.2009, p. 123-130.

Research output: Contribution to journalArticle

Zivadinov, R, Weinstock-Guttman, B, Zorzon, M, Uxa, L, Serafin, M, Bosco, A, Bratina, A, Maggiore, C, Grop, A, Tommasi, MA, Srinivasaraghavan, B & Ramanathan, M 2009, 'Gene-environment interactions between HLA B7/A2, EBV antibodies are associated with MRI injury in multiple sclerosis', Journal of Neuroimmunology, vol. 209, no. 1-2, pp. 123-130. https://doi.org/10.1016/j.jneuroim.2009.01.023
Zivadinov, Robert ; Weinstock-Guttman, Bianca ; Zorzon, Marino ; Uxa, Laura ; Serafin, Maurizia ; Bosco, Antonio ; Bratina, Alessio ; Maggiore, Cosimo ; Grop, Attilio ; Tommasi, Maria Antonietta ; Srinivasaraghavan, Bhooma ; Ramanathan, Murali. / Gene-environment interactions between HLA B7/A2, EBV antibodies are associated with MRI injury in multiple sclerosis. In: Journal of Neuroimmunology. 2009 ; Vol. 209, No. 1-2. pp. 123-130.
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abstract = "Purpose: To determine the role of gene-environmental interactions between the Class I and Class II HLA alleles and the humoral anti-Epstein-Barr Virus (EBV) responses in the development of brain injury and clinical disability in multiple sclerosis (MS) patients. Methods: A total of 93 MS patients (62 females; 31 males) and 122 healthy controls underwent HLA typing and testing for antibodies against EBV. The MS patients underwent brain MRI and quantitative measurements of T1- and T2-lesion volumes (LVs) and brain parenchymal fraction (BPF) were obtained. There were 54 MS cases that underwent MRI and EBV-antibody assessments at the 3-year follow-up. The anti-EBV panel included measurements of the levels of anti-EBV early antigen (EA) IgG, anti-EBV nuclear antigen (EBNA) IgG and anti-EBV viral capsid antigen (VCA) IgM and anti-EBV VCA IgG. The relationships between HLA alleles, anti-EBV antibody levels, MRI and clinical parameters were assessed in regression analysis. Results: The presence of HLA B7 was associated with increased T1-LV and trends indicating increased anti-EBV VCA IgG levels, higher disability (EDSS) and more destructive MRI parameters (increased T2-LV and decreased BPF). The presence of HLA A2 was associated with lower EDSS and a trend toward decreased anti-EBV VCA IgG levels; the associations with MRI variables were not significant. The HLA B7-A2 haplotype was significantly associated with higher T2-LV and T1-LV and a trend toward lower BPF was observed. Conclusions: Our data suggest that gene-environment interactions between specific HLA Class I loci and EBV exposure are associated with MRI markers of lesion injury and brain atrophy in MS patients.",
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AU - Zivadinov, Robert

AU - Weinstock-Guttman, Bianca

AU - Zorzon, Marino

AU - Uxa, Laura

AU - Serafin, Maurizia

AU - Bosco, Antonio

AU - Bratina, Alessio

AU - Maggiore, Cosimo

AU - Grop, Attilio

AU - Tommasi, Maria Antonietta

AU - Srinivasaraghavan, Bhooma

AU - Ramanathan, Murali

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N2 - Purpose: To determine the role of gene-environmental interactions between the Class I and Class II HLA alleles and the humoral anti-Epstein-Barr Virus (EBV) responses in the development of brain injury and clinical disability in multiple sclerosis (MS) patients. Methods: A total of 93 MS patients (62 females; 31 males) and 122 healthy controls underwent HLA typing and testing for antibodies against EBV. The MS patients underwent brain MRI and quantitative measurements of T1- and T2-lesion volumes (LVs) and brain parenchymal fraction (BPF) were obtained. There were 54 MS cases that underwent MRI and EBV-antibody assessments at the 3-year follow-up. The anti-EBV panel included measurements of the levels of anti-EBV early antigen (EA) IgG, anti-EBV nuclear antigen (EBNA) IgG and anti-EBV viral capsid antigen (VCA) IgM and anti-EBV VCA IgG. The relationships between HLA alleles, anti-EBV antibody levels, MRI and clinical parameters were assessed in regression analysis. Results: The presence of HLA B7 was associated with increased T1-LV and trends indicating increased anti-EBV VCA IgG levels, higher disability (EDSS) and more destructive MRI parameters (increased T2-LV and decreased BPF). The presence of HLA A2 was associated with lower EDSS and a trend toward decreased anti-EBV VCA IgG levels; the associations with MRI variables were not significant. The HLA B7-A2 haplotype was significantly associated with higher T2-LV and T1-LV and a trend toward lower BPF was observed. Conclusions: Our data suggest that gene-environment interactions between specific HLA Class I loci and EBV exposure are associated with MRI markers of lesion injury and brain atrophy in MS patients.

AB - Purpose: To determine the role of gene-environmental interactions between the Class I and Class II HLA alleles and the humoral anti-Epstein-Barr Virus (EBV) responses in the development of brain injury and clinical disability in multiple sclerosis (MS) patients. Methods: A total of 93 MS patients (62 females; 31 males) and 122 healthy controls underwent HLA typing and testing for antibodies against EBV. The MS patients underwent brain MRI and quantitative measurements of T1- and T2-lesion volumes (LVs) and brain parenchymal fraction (BPF) were obtained. There were 54 MS cases that underwent MRI and EBV-antibody assessments at the 3-year follow-up. The anti-EBV panel included measurements of the levels of anti-EBV early antigen (EA) IgG, anti-EBV nuclear antigen (EBNA) IgG and anti-EBV viral capsid antigen (VCA) IgM and anti-EBV VCA IgG. The relationships between HLA alleles, anti-EBV antibody levels, MRI and clinical parameters were assessed in regression analysis. Results: The presence of HLA B7 was associated with increased T1-LV and trends indicating increased anti-EBV VCA IgG levels, higher disability (EDSS) and more destructive MRI parameters (increased T2-LV and decreased BPF). The presence of HLA A2 was associated with lower EDSS and a trend toward decreased anti-EBV VCA IgG levels; the associations with MRI variables were not significant. The HLA B7-A2 haplotype was significantly associated with higher T2-LV and T1-LV and a trend toward lower BPF was observed. Conclusions: Our data suggest that gene-environment interactions between specific HLA Class I loci and EBV exposure are associated with MRI markers of lesion injury and brain atrophy in MS patients.

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KW - MHC

KW - Multiple sclerosis

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