Viktor Grut1, Martin Biström1, Jonatan Salzer1, Pernilla Stridh2,3, Daniel Jons4, Rasmus Gustafsson2,3, Anna Fogdell-Hahn2,3, Jesse Huang2,3, Nicole Brenner5, Julia Butt5, Noemi Bender5, Anna Lindam6, Lucia Alonso-Magdalena7, Martin Gunnarsson8, Magnus Vrethem9, Tomas Bergström10, Oluf Andersen4, Ingrid Kockum2,3, Tim Waterboer5, Tomas Olsson2,3, Peter Sundström1. 1. Department of Clinical Science, Neurosciences, Umeå University, Umeå, Sweden. 2. Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. 3. Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden. 4. Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. 5. Infections and Cancer Epidemiology Division, German Cancer Research Center (DKFZ), Heidelberg, Germany. 6. Department of Public Health and Clinical Medicine, Unit of Research, Education and Development Östersund Hospital, Umeå University, Umeå, Sweden. 7. Department of Neurology, Skåne University Hospital in Malmö/Lund and Institution of Clinical Sciences, Neurology, Lund University, Lund, Sweden. 8. Department of Neurology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden. 9. Department of Neurology and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden. 10. Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Abstract
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.
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.
Authors: Linn Persson Berg; Marcus Eriksson; Sonia Longhi; Ingrid Kockum; Clemens Warnke; Elisabeth Thomsson; Malin Bäckström; Tomas Olsson; Anna Fogdell-Hahn; Tomas Bergström Journal: BMJ Neurol Open Date: 2022-07-27
Authors: Sahl Khalid Bedri; Björn Evertsson; Mohsen Khademi; Faiez Al Nimer; Tomas Olsson; Jan Hillert; Anna Glaser Journal: Ann Clin Transl Neurol Date: 2022-05-13 Impact factor: 5.430