RESUMEN
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.
Asunto(s)
Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 6 , Esclerosis Múltiple , Adolescente , Estudios de Casos y Controles , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/epidemiología , Herpesvirus Humano 4 , Humanos , Esclerosis Múltiple/epidemiología , Factores de RiesgoRESUMEN
We here review contemporary data on genetic and environmental risk factors, particularly Epstein-Barr virus infection, for multiple sclerosis. There is an important immunogenetic etiological factor for multiple sclerosis. However, a general assumption is that immune defense genes are activated by the environment, basically by infections. We contend that the relationship between infectious mononucleosis and multiple sclerosis cannot be completely explained by genetics and inverse causality. Epstein-Barr infection as indicated by positive serology is an obligatory precondition for multiple sclerosis, which is a stronger attribute than a risk factor only. Data on events in the early pathogenesis of multiple sclerosis are cumulating from bio-banks with presymptomatic specimens, but there is only little information from the critical age when Epstein-Barr infection including infectious mononucleosis is acquired, nor on the detailed immunological consequences of this infection in individuals with and without multiple sclerosis. We discuss how focused bio-banking may elaborate a rationale for the development of treatment or vaccination against Epstein-Barr virus infection. A cohort in which intervention against Epstein-Barr infections was performed should be the object of neurological follow-up.