Epstein-Barr virus infection after adolescence and human herpesvirus 6A as risk factors for multiple sclerosis.
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.
['Biström|M|M|0000-0003-3994-2305', 'Jons|D|D|', 'Engdahl|E|E|', 'Gustafsson|R|R|', 'Huang|J|J|', 'Brenner|N|N|', 'Butt|J|J|', 'Alonso-Magdalena|L|L|', 'Gunnarsson|M|M|', 'Vrethem|M|M|', 'Bender|N|N|', 'Waterboer|T|T|', 'Granåsen|G|G|', 'Olsson|T|T|', 'Kockum|I|I|', 'Andersen|O|O|', 'Fogdell-Hahn|A|A|', 'Sundström|Peter|P|']
D000293:Adolescent D016022:Case-Control Studies D020031:Epstein-Barr Virus Infections D004854:Herpesvirus 4, Human D015654:Herpesvirus 6, Human D006801:Humans D009103:Multiple Sclerosis D012307:Risk Factors
Epstein-Barr virus human herpesvirus 6A multiple sclerosis serology case-control studies