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. 2021 Feb;28(2):579-586.
doi: 10.1111/ene.14597. Epub 2020 Nov 22.

Epstein-Barr virus infection after adolescence and human herpesvirus 6A as risk factors for multiple sclerosis

M Biström  1 , D Jons  2 , E Engdahl  3   4 , R Gustafsson  3   4 , J Huang  3   4 , N Brenner  5 , J Butt  5 , L Alonso-Magdalena  6 , M Gunnarsson  7 , M Vrethem  8 , N Bender  5 , T Waterboer  5 , G Granåsen  9 , T Olsson  3   4 , I Kockum  3   4 , O Andersen  2 , A Fogdell-Hahn  3   4 , Peter Sundström  1
Affiliations

Epstein-Barr virus infection after adolescence and human herpesvirus 6A as risk factors for multiple sclerosis

M Biström et al. Eur J Neurol. 2021 Feb.

Abstract

Background and purpose: Infections with human herpesvirus 6A (HHV-6A) and Epstein-Barr virus (EBV) have been linked to multiple sclerosis (MS) development. For EBV, late infection has been proposed as a risk factor, but serological support is lacking. The objective of this study was to investigate how age affects the EBV and HHV-6A associated risks of developing MS.

Methods: In this nested case-control study, Swedish biobanks were accessed to find pre-symptomatically collected blood samples from 670 individuals who later developed relapsing MS and 670 matched controls. A bead-based multiplex assay was used to determine serological response against EBV and HHV-6A. Conditional logistic regression was used to calculate odds ratios and 95% confidence intervals.

Results: Seropositivity against EBV exhibited a pattern where associations switched from a decreased risk of developing MS in the group below 20 years of age to an increased risk amongst individuals aged 20-29 and 30-39 years (p for trend 0.020). The age of transition was estimated to be 18.8 years. In contrast, HHV-6A was associated with increased MS risk in all age groups (total cohort odds ratio 2.1, 95% confidence interval 1.6-2.7).

Conclusions: This study suggests EBV infection after adolescence and age independent HHV-6A infection as risk factors for MS.

Keywords: Epstein-Barr virus; case-control studies; human herpesvirus 6A; multiple sclerosis; serology.

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Conflict of interest statement

M.B. has received a speaker fee from Biogen. T.O. has received grants and personal fees from Biogen, Novartis, Sanofi, Merck, Roche and Almirall, not related to this study. The other authors report no conflicts of interest.

Figures

Figure 1
Figure 1
Predicted probability of EBV seropositivity by age for cases and controls with 95% confidence intervals. Curves were estimated using logistic regression. A cut‐off of 18.8 years was calculated as the age at intersection between the two curves. EBV seropositivity is defined as seroresponse to EBNA‐1 trunc, EBNA‐1 pep or VCA p18. [Colour figure can be viewed at wileyonlinelibrary.com]
Figure 2
Figure 2
Interaction between EBV and HHV‐6A in relation to MS risk. AP, attributable proportion; OR, odds ratio. EBV seropositivity defined as seroresponse to EBNA‐1 trunc, EBNA‐1 pep or VCA p18. HHV‐6A positivity defined as reactivity against IE1A > 50 median fluorescence intensity.
See this image and copyright information in PMC

References

    1. Ascherio A, Munger K. Epidemiology of multiple sclerosis: from risk factors to prevention—an update. Semin Neurol 2016; 36: 103–114. - PubMed
    1. Olsson T, Barcellos LF, Alfredsson L. Interactions between genetic, lifestyle and environmental risk factors for multiple sclerosis. Nat Rev Neurol 2017; 13: 25–36. - PubMed
    1. Leibovitch EC, Jacobson S. Evidence linking HHV‐6 with multiple sclerosis: an update. Curr Opin Virol 2014; 9: 127–133. - PMC - PubMed
    1. Grinde B. Herpesviruses: latency and reactivation—viral strategies and host response. J Oral Microbiol 2013; 5: 22766. - PMC - PubMed
    1. Thorley‐Lawson DA. EBV persistence—introducing the virus. Curr Top Microbiol Immunol 2015; 390: 151–209. - PMC - PubMed

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