Department of Clinical Science, Neurosciences, Umeå University, Umeå, Sweden.
Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Eur J Neurol. 2021 Feb;28(2):579-586. doi: 10.1111/ene.14597. Epub 2020 Nov 22.
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.
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.
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).
This study suggests EBV infection after adolescence and age independent HHV-6A infection as risk factors for MS.
人类疱疹病毒 6A(HHV-6A)和 Epstein-Barr 病毒(EBV)感染与多发性硬化症(MS)的发展有关。对于 EBV,有人提出晚期感染是一个危险因素,但缺乏血清学支持。本研究旨在探讨年龄如何影响 EBV 和 HHV-6A 引发 MS 的风险。
在这项巢式病例对照研究中,我们访问了瑞典生物库,以寻找 670 名随后发生复发性 MS 的个体和 670 名匹配对照者在出现症状前采集的血液样本。采用基于珠的多重分析来确定针对 EBV 和 HHV-6A 的血清反应。采用条件逻辑回归计算比值比和 95%置信区间。
针对 EBV 的血清阳性率呈现出一种模式,即关联在 20 岁以下人群中从 MS 发病风险降低转变为 20-29 岁和 30-39 岁人群中风险增加(趋势检验的 p 值为 0.020)。估计的年龄转折点为 18.8 岁。相比之下,HHV-6A 在所有年龄组中均与 MS 风险增加相关(总队列的比值比为 2.1,95%置信区间为 1.6-2.7)。
本研究提示青春期后 EBV 感染和年龄独立的 HHV-6A 感染是 MS 的危险因素。