Risk of a first clinical diagnosis of central nervous system demyelination in relation to human herpesviruses in the context of Epstein–Barr virus
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(Published version)
Date
2023
Authors
Lucas, R.M.
Lay, M.L.J.
Grant, J.
Cherbuin, N.
Toi, C.S.
Dear, K.
Taylor, B.V.
Dwyer, D.E.
Chapman, C.
Coulthard, A.
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Journal article
Citation
European Journal of Neurology, 2023; 30(9):2752-2760
Statement of Responsibility
Robyn M. Lucas, Meav-Lang J. Lay, James Grant, Nicolas Cherbuin, Cheryl S. Toi, Keith Dear, Bruce V. Taylor, Dominic E. Dwyer, Ausimmune Investigator Group, Anne-Louise Ponsonby
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Abstract
Background and purpose: Epstein–Barr virus (EBV) is implicated in multiple sclerosis (MS) risk; evidence for other herpesviruses is inconsistent. Here, we test blood markers of infection with human herpesvirus 6 (HHV-6), varicella zoster virus (VZV), and cytomegalovirus (CMV) as risk factors for a first clinical diagnosis of central nervous system demyelination (FCD) in the context of markers of EBV infection. Methods: In the Ausimmune case–control study, cases had an FCD, and population controls were matched on age, sex, and study region. We quantified HHV-6- and VZVDNA load in whole blood and HHV-6, VZV, and CMV antibodies in serum. Conditional logistic regression tested associations with FCD risk, adjusting for Epstein–Barr nuclear antigen (EBNA) IgG, EBV-DNA load, and other covariates. Results: In 204 FCD cases and 215 matched controls, only HHV-6-DNA load (positive vs. negative) was associated with FCD risk (adjusted odds ratio = 2.20, 95% confidence interval = 1.08–4.46, p= 0.03). Only EBNA IgG and HHV-6-DNA positivity were retained in a predictive model of FCD risk; the combination had a stronger association than either alone. CMV-specific IgG concentration modified the association between an MS riskrelated human leucocyte antigen gene and FCD risk. Six cases and one control had very high HHV-6-DNA load (>1.0 × 106 copies/mL). Conclusions: HHV-6-DNA positivity and high load (possibly due to inherited HHV-6 chromosomal integration) were associated with increased FCD risk, particularly in association with markers of EBV infection. With growing interest in prevention/ management of MS through EBV-related pathways, there should be additional consideration of the role of HHV-6 infection.
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Dissertation Note
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Published September 2023
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© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.