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

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.