High Levels of Epstein–Barr Virus Nuclear Antigen-1-Specific Antibodies and Infectious Mononucleosis Act Both Independently and Synergistically to Increase Multiple Sclerosis Risk

Hedström, Anna Karin; Huang, Jesse; Michel, Angelica; Butt, Julia; Brenner, Nicole; Hillert, Jan; Waterboer, Tim; Kockum, Ingrid; Olsson, Tomas; Alfredsson, Lars

doi:10.3389/fneur.2019.01368

Cited by 61 publications

(70 citation statements)

References 31 publications

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“…In addition, the prevalence and HHV-6 antibody level between MS patients and controls was not statistically significant. These results must be interpreted with caution as they are in conflict with multiple reports from other countries [ 51 – 53 ]. The absence of association between MS and EBV seropositivity in our study could be attributed to the extremely high seropositivity rate in the normal control population (98%).…”

Section: Discussioncontrasting

confidence: 73%

Prevalence of seropositivity of selected herpesviruses in patients with multiple sclerosis in the North of Jordan

Kofahi

Sabaheen

et al. 2020

BMC Neurol

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Background Multiple sclerosis (MS) is a neurological disease that is caused by an autoimmune response that results in the neuron’s demyelination in the central nervous system. The exact etiology of MS is not clear; however, several environmental and genetic factors are believed to participate in its initiation and development, including exposure to viruses. This study aims to investigate the association between the seropositivity and antibody titer of selected herpesviruses and MS in Jordanian MS patients. Method In this study, 55 MS patients and 40 age- and gender-matching apparently healthy volunteers were recruited from two main hospitals in the north of Jordan. MS patients were grouped into three types of MS based on the clinical presentation of the disease. Blood samples were collected from the participants and the IgG antibodies for human herpesvirus 6 (HHV-6), Epstein-Barr virus (EBV) nuclear antigen (EBNA), EBV viral capsid antigen (VCA) and varicella-zoster virus (VZV) were assayed by ELISA. The prevalence of seropositivity and the antibody level for each of the antibodies were compared between MS patients and controls and between the three types of MS. Results There was no significant difference in the prevalence of seropositivity and in the levels of antibodies for HHV-6, EBNA and VCA between MS patients and controls and between the three types of MS. In contrast, the number of seropositive patients and the level of IgG antibodies for VZV were significantly higher in MS patients compared to the control. Conclusion This study showed that patients with MS in the north of Jordan were more likely to be seropositive for VZV than the general population. Based on this finding, we recommend further studies to evaluate the seropositivity to VZV to be carried out in other parts of Jordan and the greater middle east to find out if there is a correlation between MS and previous infection with VZV.

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Section: Discussioncontrasting

confidence: 73%

Prevalence of seropositivity of selected herpesviruses in patients with multiple sclerosis in the North of Jordan

Kofahi

Sabaheen

et al. 2020

BMC Neurol

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show abstract

“…Our results did not find a significant difference in the prevalence and levels of EBV and HHV-6 antibodies between MS patients and controls. These results must be interpreted with caution as they are in conflict with multiple reports from other countries [50][51][52]. The absence of association between MS and EBV seropositivity in our study could be attributed to the extremely high rate of seropositivity in the normal control population (98%).…”

Section: Discussioncontrasting

confidence: 94%

Prevalence of seropositivity of selected Herpesviruses in patients with Multiple Sclerosis in the North of Jordan

Kofahi

Sabaheen

et al. 2020

Preprint

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BackgroundMultiple sclerosis (MS) is a neurological disease that is caused by an autoimmune response that results in the demyelination of the neurons in the central nervous system. The exact etiology of MS is not clear; however, several environmental and genetic factors are believed to participate in its initiation and development, including exposure to viruses.AimThe aim of this study is to investigate the association between the seropositivity and antibody titer of selected herpesviruses and MS in Jordanian MS patients.MethodIn this study, 55 MS patients and 40 age- and gender-matching apparently healthy volunteers were recruited from two main hospitals in the north of Jordan. MS patients were grouped into three types of MS based on the clinical presentation of the disease. Blood samples were collected from the participants and the IgG antibodies for human herpes virus 6 (HHV-6), Epstein Barr virus (EBV) nuclear antigen (EBNA), EBV viral capsid antigen (VCA) and varicella zoster virus (VZV) were assayed by ELISA. The prevalence of seropositivity and the antibody level for each of the antibodies were compared between MS patients and controls and between the three types of MS.ResultsThere was no significant difference in the prevalence of seropositivity and in the levels of antibodies for HHV-6, EBNA and VCA between MS patients and controls and between the three types of MS. In contrast, the number of seropositive patients and the level of IgG antibodies for VZV were significantly higher in MS patients compared to the control.ConclusionThis study showed that patients with MS in the north of Jordan were more likely to be seropositive for VZV than the general population. Based on this finding, we recommend further studies to evaluate the seropositivity to VZV to be carried out in other parts of Jordan and the greater middle east to find out if there is correlation between MS and previous infection with VZV.

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“…A recent study showed that HLA-DRB1*1501 carriership also in healthy controls, fully unrelated to patients with MS, is associated with enhanced EBNA-1 IgG levels. 23 The high prevalence of HLA-DRB1*1501 in patients with MS, intermediate in siblings, and low in spouses could partly explains the gradient observed in EBNA-1 IgG titers in the 3 groups. After stratification for HLA-DRB1*1501, the observed gradient was still present in young patients with MS, siblings and spouses.…”

Section: Discussionmentioning

confidence: 96%

EBNA-1 titer gradient in families with multiple sclerosis indicates a genetic contribution

Mescheriakova

Nierop

Eijk

et al. 2020

Neurol Neuroimmunol Neuroinflamm

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ObjectiveIn multiplex MS families, we determined the humoral immune response to Epstein-Barr virus nuclear antigen 1 (EBNA-1)-specific immunoglobulin γ (IgG) titers in patients with MS, their healthy siblings, and biologically unrelated healthy spouses and investigated the role of specific genetic loci on the antiviral IgG titers.MethodsIgG levels against EBNA-1 and varicella zoster virus (VZV) as control were measured. HLA-DRB1*1501 and HLA-A*02 tagging single-nucleotide polymorphisms (SNPs) were genotyped. We assessed the associations between these SNPs and antiviral IgG titers.ResultsOR for abundant EBNA-1 IgG was the highest in patients with MS and intermediate in their siblings compared with spouses. We confirmed that HLA-DRB1*1501 is associated with abundant EBNA-1 IgG. After stratification for HLA-DRB1*1501, the EBNA-1 IgG gradient was still significant in patients with MS and young siblings compared with spouses. HLA-A*02 was not explanatory for EBNA-1 IgG titer gradient. No associations for VZV IgG were found.ConclusionsIn families with MS, the EBNA-1 IgG gradient being the highest in patients with MS, intermediate in their siblings, and lowest in biologically unrelated spouses indicates a genetic contribution to EBNA-1 IgG levels that is only partially explained by HLA-DRB1*1501 carriership.

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High Levels of Epstein–Barr Virus Nuclear Antigen-1-Specific Antibodies and Infectious Mononucleosis Act Both Independently and Synergistically to Increase Multiple Sclerosis Risk

Cited by 61 publications

References 31 publications

Prevalence of seropositivity of selected herpesviruses in patients with multiple sclerosis in the North of Jordan

Prevalence of seropositivity of selected herpesviruses in patients with multiple sclerosis in the North of Jordan

Prevalence of seropositivity of selected Herpesviruses in patients with Multiple Sclerosis in the North of Jordan

EBNA-1 titer gradient in families with multiple sclerosis indicates a genetic contribution

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