PMID- 34107122 OWN - NLM STAT- MEDLINE DCOM- 20211018 LR - 20211018 IS - 1468-1331 (Electronic) IS - 1351-5101 (Linking) VI - 28 IP - 9 DP - 2021 Sep TI - Cytomegalovirus seropositivity is associated with reduced risk of multiple sclerosis-a presymptomatic case-control study. PG - 3072-3079 LID - 10.1111/ene.14961 [doi] AB - BACKGROUND AND PURPOSE: Epstein-Barr virus (EBV) and human herpesvirus 6A (HHV-6A) are associated with increased risk of multiple sclerosis (MS). Conversely, infection with cytomegalovirus (CMV) has been suggested to reduce the risk of MS but supporting data from presymptomatic studies are lacking. Here, it was sought to increase the understanding of CMV in MS aetiology. METHODS: A nested case-control study was performed with presymptomatically collected blood samples identified through crosslinkage of MS registries and Swedish biobanks. Serological antibody response against CMV, EBV and HHV-6A was determined using a bead-based multiplex assay. Odds ratio (OR) with 95% confidence interval (CI) for CMV seropositivity as a risk factor for MS was calculated by conditional logistic regression and adjusted for EBV and HHV-6A seropositivity. Potential interactions on the additive scale were analysed by calculating the attributable proportion due to interaction (AP). RESULTS: Serum samples from 670 pairs of matched cases and controls were included. CMV seropositivity was associated with a reduced risk for MS (OR = 0.70, 95% CI 0.56-0.88, p = 0.003). Statistical interactions on the additive scale were observed between seronegativity for CMV and seropositivity against HHV-6A (AP 0.34, 95% CI 0.06-0.61) and EBV antigen EBNA-1 (amino acid 385-420) at age 20-39 years (AP 0.37, 95% CI 0.09-0.65). CONCLUSIONS: Cytomegalovirus seropositivity is associated with a decreased risk for MS. The protective role for CMV infection in MS aetiology is further supported by the interactions between CMV seronegativity and EBV and HHV-6A seropositivity. CI - (c) 2021 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology. FAU - Grut, Viktor AU - Grut V AUID- ORCID: 0000-0002-5415-6567 AD - Department of Clinical Science, Neurosciences, Umea University, Umea, Sweden. FAU - Bistrom, Martin AU - Bistrom M AUID- ORCID: 0000-0003-3994-2305 AD - Department of Clinical Science, Neurosciences, Umea University, Umea, Sweden. FAU - Salzer, Jonatan AU - Salzer J AUID- ORCID: 0000-0002-9205-0771 AD - Department of Clinical Science, Neurosciences, Umea University, Umea, Sweden. FAU - Stridh, Pernilla AU - Stridh P AD - Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. AD - Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden. FAU - Jons, Daniel AU - Jons D AD - Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. FAU - Gustafsson, Rasmus AU - Gustafsson R AD - Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. AD - Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden. FAU - Fogdell-Hahn, Anna AU - Fogdell-Hahn A AD - Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. AD - Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden. FAU - Huang, Jesse AU - Huang J AD - Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. AD - Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden. FAU - Brenner, Nicole AU - Brenner N AD - Infections and Cancer Epidemiology Division, German Cancer Research Center (DKFZ), Heidelberg, Germany. FAU - Butt, Julia AU - Butt J AD - Infections and Cancer Epidemiology Division, German Cancer Research Center (DKFZ), Heidelberg, Germany. FAU - Bender, Noemi AU - Bender N AD - Infections and Cancer Epidemiology Division, German Cancer Research Center (DKFZ), Heidelberg, Germany. FAU - Lindam, Anna AU - Lindam A AD - Department of Public Health and Clinical Medicine, Unit of Research, Education and Development Ostersund Hospital, Umea University, Umea, Sweden. FAU - Alonso-Magdalena, Lucia 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, Martin AU - Gunnarsson M AD - Department of Neurology, Faculty of Medicine and Health, Orebro University, Orebro, Sweden. FAU - Vrethem, Magnus AU - Vrethem M AD - Department of Neurology and Department of Clinical and Experimental Medicine, Linkoping University, Linkoping, Sweden. FAU - Bergstrom, Tomas AU - Bergstrom T AD - Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. FAU - Andersen, Oluf AU - Andersen O AD - Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. FAU - Kockum, Ingrid AU - Kockum I AD - Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. AD - Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden. FAU - Waterboer, Tim AU - Waterboer T AD - Infections and Cancer Epidemiology Division, German Cancer Research Center (DKFZ), Heidelberg, Germany. FAU - Olsson, Tomas AU - Olsson T AD - Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. AD - Center for Molecular Medicine, Karolinska University Hospital, 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 - 20210627 PL - England TA - Eur J Neurol JT - European journal of neurology JID - 9506311 SB - IM MH - Adult MH - Case-Control Studies MH - Cytomegalovirus MH - *Epstein-Barr Virus Infections/complications/epidemiology MH - Herpesvirus 4, Human MH - Humans MH - *Multiple Sclerosis/epidemiology MH - Young Adult OTO - NOTNLM OT - case-control studies OT - cytomegalovirus OT - herpesviruses OT - multiple sclerosis OT - serology EDAT- 2021/06/10 06:00 MHDA- 2021/10/21 06:00 CRDT- 2021/06/09 17:34 PHST- 2021/05/12 00:00 [revised] PHST- 2021/03/02 00:00 [received] PHST- 2021/06/07 00:00 [accepted] PHST- 2021/06/10 06:00 [pubmed] PHST- 2021/10/21 06:00 [medline] PHST- 2021/06/09 17:34 [entrez] AID - 10.1111/ene.14961 [doi] PST - ppublish SO - Eur J Neurol. 2021 Sep;28(9):3072-3079. doi: 10.1111/ene.14961. Epub 2021 Jun 27.