PMID- 33065762 OWN - NLM STAT- MEDLINE DCOM- 20210812 LR - 20210812 IS - 1468-1331 (Electronic) IS - 1351-5101 (Print) IS - 1351-5101 (Linking) VI - 28 IP - 2 DP - 2021 Feb TI - Epstein-Barr virus infection after adolescence and human herpesvirus 6A as risk factors for multiple sclerosis. PG - 579-586 LID - 10.1111/ene.14597 [doi] AB - 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. CI - (c) 2020 The Authors. European Journal of Neurology Published by John Wiley & Sons Ltd on behalf of European Academy of Neurology. FAU - Bistrom, M AU - Bistrom M AUID- ORCID: 0000-0003-3994-2305 AD - Department of Clinical Science, Neurosciences, Umea University, Umea, Sweden. FAU - Jons, D AU - Jons D AD - Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. FAU - Engdahl, E AU - Engdahl E AD - Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. AD - Center for Molecular Medicine, Stockholm, Sweden. FAU - Gustafsson, R AU - Gustafsson R AD - Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. AD - Center for Molecular Medicine, Stockholm, Sweden. FAU - Huang, J AU - Huang J AD - Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. AD - Center for Molecular Medicine, Stockholm, Sweden. FAU - Brenner, N AU - Brenner N AD - Infections and Cancer Epidemiology, German Cancer Research Center (Deutsches Krebsforschungszentrum), Heidelberg, Germany. FAU - Butt, J AU - Butt J AD - Infections and Cancer Epidemiology, German Cancer Research Center (Deutsches Krebsforschungszentrum), Heidelberg, Germany. FAU - Alonso-Magdalena, L AU - Alonso-Magdalena L AD - Department of Neurology, Skane University Hospital in Malmo/Lund and Institution of Clinical Sciences, Neurology, Lund University, Lund, Sweden. FAU - Gunnarsson, M AU - Gunnarsson M AD - School of Medical Sciences, Orebro University, Orebro, Sweden. FAU - Vrethem, M AU - Vrethem M AD - Department of Neurology and Department of Clinical and Experimental Medicine, Linkoping University, Linkoping, Sweden. FAU - Bender, N AU - Bender N AD - Infections and Cancer Epidemiology, German Cancer Research Center (Deutsches Krebsforschungszentrum), Heidelberg, Germany. FAU - Waterboer, T AU - Waterboer T AD - Infections and Cancer Epidemiology, German Cancer Research Center (Deutsches Krebsforschungszentrum), Heidelberg, Germany. FAU - Granasen, G AU - Granasen G AD - Department of Public Health and Clinical Medicine, Umea University, Umea, Sweden. FAU - Olsson, T AU - Olsson T AD - Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. AD - Center for Molecular Medicine, Stockholm, Sweden. FAU - Kockum, I AU - Kockum I AD - Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. AD - Center for Molecular Medicine, Stockholm, Sweden. FAU - Andersen, O AU - Andersen O AD - Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. FAU - Fogdell-Hahn, A AU - Fogdell-Hahn A AD - Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. AD - Center for Molecular Medicine, Stockholm, Sweden. FAU - Sundstrom, Peter AU - Sundstrom P AD - Department of Clinical Science, Neurosciences, Umea University, Umea, Sweden. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20201122 PL - England TA - Eur J Neurol JT - European journal of neurology JID - 9506311 SB - IM MH - Adolescent MH - Case-Control Studies MH - *Epstein-Barr Virus Infections/complications/epidemiology MH - Herpesvirus 4, Human MH - *Herpesvirus 6, Human MH - Humans MH - *Multiple Sclerosis/epidemiology MH - Risk Factors PMC - PMC7839468 OTO - NOTNLM OT - Epstein-Barr virus OT - case-control studies OT - human herpesvirus 6A OT - multiple sclerosis OT - serology COIS- 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. EDAT- 2020/10/17 06:00 MHDA- 2021/08/13 06:00 PMCR- 2021/01/27 CRDT- 2020/10/16 20:19 PHST- 2020/06/16 00:00 [received] PHST- 2020/10/06 00:00 [accepted] PHST- 2020/10/17 06:00 [pubmed] PHST- 2021/08/13 06:00 [medline] PHST- 2020/10/16 20:19 [entrez] PHST- 2021/01/27 00:00 [pmc-release] AID - ENE14597 [pii] AID - 10.1111/ene.14597 [doi] PST - ppublish SO - Eur J Neurol. 2021 Feb;28(2):579-586. doi: 10.1111/ene.14597. Epub 2020 Nov 22.