open access

Vol 56, No 3 (2022)
Research Paper
Submitted: 2022-03-16
Accepted: 2022-05-24
Published online: 2022-06-21
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Anti-EBNA1 IgG titre is not associated with fatigue in multiple sclerosis patients

Michael Fleischer12, Helene Schuh12, Nela M. Bickmann12, Tim Hagenacker12, Karlgeorg Krüger3, Thomas Skripuletz4, Melanie Fiedler5, Christoph Kleinschnitz12, Refik Pul12, Jelena Skuljec12
·
Pubmed: 35726751
·
Neurol Neurochir Pol 2022;56(3):236-245.
Affiliations
  1. Department of Neurology, University Medicine Essen, Essen, Germany
  2. Centre for Translational Neuro- and Behavioural Sciences (C-TNBS), University Medicine Essen, Essen, Germany
  3. Diavero Diagnosis Centre, Essen, Germany
  4. Department of Neurology, Hanover Medical School, Hanover, Germany
  5. Institute for Virology, University Medicine Essen, Essen, Germany

open access

Vol 56, No 3 (2022)
RESEARCH PAPERS — LEADING TOPIC
Submitted: 2022-03-16
Accepted: 2022-05-24
Published online: 2022-06-21

Abstract

Introduction. Fatigue is the most frequent symptom in multiple sclerosis (MS), although it is still poorly understood due to its complexity and subjective nature. There is an urgent need to identify reliable biomarkers to improve disease prognosis and therapeutic strategies. Epstein-Barr virus (EBV) is the major environmental risk factor associated with MS aetiology, and trials with EBV-targeted T cell therapies have reduced fatigue severity in MS patients.

Aim of the study. We investigated whether the serum amount of immunoglobulin (Ig)G-specific for EBV antigens could be a suitable prognostic marker for the assessment of MS-related fatigue.

Material and methods. A total of 194 MS patients were enrolled. We quantified EBV nuclear antigen 1 (EBNA1) and EBV viral capsid antigen (VCA) immunoglobulin (Ig) G levels and B cell-activating factor of the tumour necrosis factor family (BAFF) concentration in the serum of patients with relapsing-remitting MS (RRMS) and chronic progressive MS (CPMS), and we analysed their correlation with aspects of fatigue and other clinical disease parameters.

Results. A complete EBV seropositivity could be detected in our cohort. After adjusting for confounding variables and covariates, neither EBNA1 nor VCA antibody titres were associated with levels of fatigue, sleepiness, depression, or with any of the clinical values such as expanded disability status scale, lesion count, annual relapse rate, or disease duration. However, patients with RRMS had significantly higher EBNA1 IgG titre than those with CPMS, whereas this was not the case under therapies targeting CD20+ cells. BAFF levels in serum were inversely proportional to anti-EBNA1 IgG.

Conclusions and clinical implications. Our results show that EBNA1 IgG titre is not associated with the presence or level of fatigue. Whether the increased EBNA1 titre in RRMS plays a direct role in disease progression, or is only a consequence of excessive B cell activation, remains to be answered in future studies.

Abstract

Introduction. Fatigue is the most frequent symptom in multiple sclerosis (MS), although it is still poorly understood due to its complexity and subjective nature. There is an urgent need to identify reliable biomarkers to improve disease prognosis and therapeutic strategies. Epstein-Barr virus (EBV) is the major environmental risk factor associated with MS aetiology, and trials with EBV-targeted T cell therapies have reduced fatigue severity in MS patients.

Aim of the study. We investigated whether the serum amount of immunoglobulin (Ig)G-specific for EBV antigens could be a suitable prognostic marker for the assessment of MS-related fatigue.

Material and methods. A total of 194 MS patients were enrolled. We quantified EBV nuclear antigen 1 (EBNA1) and EBV viral capsid antigen (VCA) immunoglobulin (Ig) G levels and B cell-activating factor of the tumour necrosis factor family (BAFF) concentration in the serum of patients with relapsing-remitting MS (RRMS) and chronic progressive MS (CPMS), and we analysed their correlation with aspects of fatigue and other clinical disease parameters.

Results. A complete EBV seropositivity could be detected in our cohort. After adjusting for confounding variables and covariates, neither EBNA1 nor VCA antibody titres were associated with levels of fatigue, sleepiness, depression, or with any of the clinical values such as expanded disability status scale, lesion count, annual relapse rate, or disease duration. However, patients with RRMS had significantly higher EBNA1 IgG titre than those with CPMS, whereas this was not the case under therapies targeting CD20+ cells. BAFF levels in serum were inversely proportional to anti-EBNA1 IgG.

Conclusions and clinical implications. Our results show that EBNA1 IgG titre is not associated with the presence or level of fatigue. Whether the increased EBNA1 titre in RRMS plays a direct role in disease progression, or is only a consequence of excessive B cell activation, remains to be answered in future studies.

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Keywords

multiple sclerosis, RRMS, progressive MS, EBV, EBNA1, fatigue, BAFF

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About this article
Title

Anti-EBNA1 IgG titre is not associated with fatigue in multiple sclerosis patients

Journal

Neurologia i Neurochirurgia Polska

Issue

Vol 56, No 3 (2022)

Article type

Research Paper

Pages

236-245

Published online

2022-06-21

Page views

4949

Article views/downloads

778

DOI

10.5603/PJNNS.a2022.0043

Pubmed

35726751

Bibliographic record

Neurol Neurochir Pol 2022;56(3):236-245.

Keywords

multiple sclerosis
RRMS
progressive MS
EBV
EBNA1
fatigue
BAFF

Authors

Michael Fleischer
Helene Schuh
Nela M. Bickmann
Tim Hagenacker
Karlgeorg Krüger
Thomas Skripuletz
Melanie Fiedler
Christoph Kleinschnitz
Refik Pul
Jelena Skuljec

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