Evidence of aberrant anti-epstein-barr virus antibody response, though no viral reactivation, in people with post-stroke fatigue

Isobel C Mouat; Li Zhu; Alperen Aslan; Barry W McColl; Stuart M Allan; Craig J Smith; Marion S Buckwalter; Laura McCulloch

doi:10.1186/s12950-024-00402-0

Evidence of aberrant anti-epstein-barr virus antibody response, though no viral reactivation, in people with post-stroke fatigue

J Inflamm (Lond). 2024 Aug 12;21(1):30. doi: 10.1186/s12950-024-00402-0.

Authors

Isobel C Mouat¹, Li Zhu², Alperen Aslan², Barry W McColl³, Stuart M Allan^{4

5

6}, Craig J Smith^{4

6

7

8}, Marion S Buckwalter^{2

9

10}, Laura McCulloch¹¹

Affiliations

¹ Centre for Inflammation Research, Institute for Regeneration and Repair South, University of Edinburgh, Edinburgh, UK.
² Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, USA.
³ UK Dementia Research Institute, Centre for Discovery Brain Sciences, The University of Edinburgh, Edinburgh, UK.
⁴ Geoffrey Jefferson Brain Research Centre, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK.
⁵ Division of Neuroscience, The University of Manchester, Manchester, UK.
⁶ Lydia Becker Institute of Immunology and Inflammation, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK.
⁷ Division of Cardiovascular Sciences, The University of Manchester, Manchester, UK.
⁸ Geoffrey Jefferson Brain Research Centre, Manchester Academic Health Science Centre, Northern Care Alliance NHS Foundation Trust, University of Manchester, Manchester, UK.
⁹ Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA.
¹⁰ Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA.
¹¹ Centre for Inflammation Research, Institute for Regeneration and Repair South, University of Edinburgh, Edinburgh, UK. laura.mcculloch@ed.ac.uk.

Abstract

Background: Fatigue is a common complication of stroke that has a significant impact on quality of life. The biological mechanisms that underly post-stroke fatigue are currently unclear, however, reactivation of latent viruses and their impact on systemic immune function have been increasingly reported in other conditions where fatigue is a predominant symptom. Epstein-Barr virus (EBV) in particular has been associated with fatigue, including in long-COVID and myalgic encephalomyelitis/chronic fatigue syndrome, but has not yet been explored within the context of stroke.

Aims: We performed an exploratory analysis to determine if there is evidence of a relationship between EBV reactivation and post-stroke fatigue.

Methods: In a chronic ischemic stroke cohort (> 5 months post-stroke), we assayed circulating EBV by qPCR and measured the titres of anti-EBV antibodies by ELISA in patients with high fatigue (FACIT-F < 40) and low fatigue (FACIT-F > 41). Statistical analysis between two-groups were performed by t-test when normally distributed according to the Shapiro-Wilk test, by Mann-Whitney test when the data was not normally distributed, and by Fisher's exact test for categorical data.

Results: We observed a similar incidence of viral reactivation between people with low versus high levels of post-stroke fatigue (5 of 22 participants (24%) versus 6 of 22 participants (27%)). Although the amount of circulating EBV was similar, we observed an altered circulating anti-EBV antibody profile in participants with high fatigue, with reduced IgM against the Viral Capsid Antigen (2.244 ± 0.926 vs. 3.334 ± 2.68; P = 0.031). Total IgM levels were not different between groups indicating this effect was specific to anti-EBV antibodies (3.23 × 10⁵ ± 4.44 × 10⁴ high fatigue versus 4.60 × 10⁵ ± 9.28 × 10⁴ low fatigue; P = 0.288).

Conclusions: These data indicate that EBV is not more prone to reactivation during chronic stroke recovery in those with post-stroke fatigue. However, the dysregulated antibody response to EBV may be suggestive of viral reactivation at an earlier stage after stroke.

Keywords: Epstein-Barr virus; Fatigue; Ischaemic stroke.

Abstract

Grants and funding