EBNA-1 and VCA-p18 immunoglobulin markers link Epstein-Barr virus immune response and brain’s myelin content to fatigue, 2024, Gayer

https://www.sciencedirect.com/science/article/pii/S2666354624001741

Mihály Gayer, Zhi Ming Xu, Flavia Hodel, Martin Preisig, Marie-Pierre F. Strippoli, Peter Vollenweider, Julien Vaucher, Antoine Lutti, Ferath Kherif, Iris-Katharina Penner, Renaud Du Pasquier, Jacques Fellay, Bogdan Draganski,
EBNA-1 and VCA-p18 immunoglobulin markers link Epstein-Barr virus immune response and brain’s myelin content to fatigue in a community-dwelling cohort,
Brain, Behavior, & Immunity - Health,
2024,
100896,
ISSN 2666-3546,
https://doi.org/10.1016/j.bbih.2024.100896.
1
LREN, Centre for Research in Neurosciences, Department of Clinical Neurosciences, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
2
Neurology service, Department of Clinical Neurosciences, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
3
Psychiatric Epidemiology and Psychopathology Research Centre, Department of Psychiatry, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
4
Division of Internal Medicine, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
5
Division of Internal Medicine, Department of Medicine and Specialties, Fribourg Hospital and University of Fribourg, Fribourg, Switzerland
6
Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
7
School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
8
Swiss Institute of Bioinformatics, Lausanne, Switzerland
9
Precision Medicine Unit, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
10
Neurology Department, Max-Planck-Institute for Human Cognitive and Brain Sciences, Leipzig, Germany
Received 27 October 2024, Accepted 27 October 2024, Available online 9 November 2024.



https://doi.org/10.1016/j.bbih.2024.100896
open access

Highlights

• •
  Population-based cohort study tested associations between EBV immune response, fatigue, and brain anatomy.
• •
  EBNA-1 IgG are associated with individuals’ fatigue levels.
• •
  VCA p18 IgG correlate with higher brain myelin content driven by male participants.
• •
  No association between brain myelin differences, MS polygenic risk score and EBV immune response.
• •
  EBV immune response may relate to fatigue levels and brain myelin in adulthood.

Abstract

Given the association of Epstein-Barr virus (EBV) with subjective perception of fatigue and demyelination in clinical conditions, the question about potential subclinical effects in the adult general population remains open.

We investigate the association between individuals’ EBV immune response and perceived fatigue in a community dwelling cohort (n=864, age 62 ± 10 years old; 49% women) while monitoring brain tissue properties.

Fatigue levels are assessed with the established fatigue severity scale, the EBNA-1 and VCA p18 immunoglobulin G (IgG) chronic response – with multiplex serology and the estimates of local brain volume, myelin content, and axonal density - using relaxometry- and multi-shell diffusion-based magnetic resonance imaging (MRI).

In our analysis we adjust for the effects of demographic and cardiovascular risk factors, sleep apnea, depression, and polygenic risk score for multiple sclerosis.

We demonstrate that EBNA-1 IgG levels are positively associated with perceived levels of fatigue, whilst VCA p18 IgG levels show a positive correlation with myelin content and a negative one with an estimate of axonal g-ratio in male participants.

In the context of EBVs immune response, the polygenic risk for multiple sclerosis is not associated with increased fatigue levels, brain myelination or atrophy.

Our findings bring empirical evidence about the potential role of EBVs chronic immune response in perceived fatigue and hint towards a protective role of myelination specific for men.

They underscore the added value of advanced assessment of brain tissue microstructure in uncovering the mechanisms behind frequent fatigue complaints associated with EBV infection and multiple sclerosis.

Keywords
Epstein-Barr virus (EBV)
Fatigue
Demyelination
Neuroimaging
Multiple sclerosis (MS)
EBV immune response
Population-based cohort study
qMRI
Brain microstructure
Magnetization transfer saturation