Serological response against HHV-6A is associated with increased risk for multiple sclerosis
ECTRIMS Online Library. Fogdell-Hahn A. 09/12/19; 279502; 222
Anna Fogdell-Hahn
Anna Fogdell-Hahn

Abstract: 222

Type: Scientific Session

Abstract Category: Pathology and pathogenesis of MS - Microbiology and virology

E. Engdahl1, R. Gustafsson1, J. Huang1, M. Biström2, I. Lima Bomfim1, P. Stridh1, M. Khademi1, N. Brenner3, J. Butt3, A. Michel3, D. Jons4, M. Hortlund1, L. Alonso-Magdalena5, A.K. Hedström1, L. Flamand6, M. Ihira7, T. Yoshikawa7, O. Andersen4, J. Hillert1, L. Alfredsson1, T. Waterboer3, P. Sundström2, T. Olsson1, I. Kockum1, A. Fogdell-Hahn8

1Karolinska Institutet, Stockholm, 2Umeå Universitet, Umeå, Sweden, 3German Cancer Research Center (DKFZ), Heidelberg, Germany, 4Sahlgrenska Academy, University of Gothenburg, Göteborg, 5Skåne University Hospital, Malmö, Sweden, 6Laval University, Québec, QC, Canada, 7Fujita Health University School of Medicine, Toyoake, Japan, 8Karlinska Institutet, Clinical Neuroscience, Clinical Neurimmunology, Karlinska Institutet, Stockholm, Sweden

Background: Human herpesvirus (HHV)-6A or HHV-6B involvement in multiple sclerosis (MS) etiology has remained controversial. By using a novel serology method, we investigated this further in a large national case-control cohort and in persons before MS disease onset.
Methods: A multiplex serological assay measuring IgG reactivity against the immediate- early protein 1 (IE1) from HHV-6A (IE1A) and -6B (IE1B) from HHV-6B was used in a MS cohort (8742 persons with MS and 7215 matched controls), and a pre-MS cohort (478 individuals and 476 matched controls). Adjusted linear and logistic regression models were conducted to investigate associations to MS. Genome-wide association analyses were performed and associations with HLA haplotypes were investigated.
Results: The IgG response against IE1A was positively associated with MS (OR = 1.55, p = 9x10-22), and with increased risk of future MS (OR = 2.22, p = 2x10-5). An interaction was observed between IE1A and Epstein-Barr virus (EBV) antibody responses on MS risk (attributable proportion = 0.24, p = 6x10-6). In contrast, the IgG response against IE1B was negatively associated with MS in the established MS cohort (OR = 0.74, p = 6x10-11). The genetic control of HHV-6 antibody response was located to the HLA region.
Conclusions: Increased serological response against HHV-6A, but not HHV-6B, IE1 proteins with an interaction with EBV and association to HLA complex genes supports a role for HHV-6A in MS etiology.
Disclosure: Swedish Research Council (grant no 2015-02419), Swedish Brain Foundation, KAW Foundation, Margareta af Ugglas Foundation. J Huang, P Stridh and I Kockum were supported partly by funding from MultipleMS Horizon 2020 grant number 733161. J Huang was also partly supported by EndMS doctoral studentship EGID: 3045 from the Multiple Sclerosis society of Canada.
Elin Engdahl: nothing to disclose
Rasmus Gustafsson: nothing to disclose
Jesse Huang: nothing to disclose
Martin Biström: nothing to disclose
Izaura Lima Bomfim: nothing to disclose
Pernilla Strid: nothing to disclose
Mohsen Khademi: nothing to disclose
Nicole Brenner: nothing to disclose
Julia Butt: nothing to disclose
Angelika Michel: nothing to disclose
Daniel Jons: nothing to disclose
Maria Hortlund: nothing to disclose
Lucia Alonso-Magdalena: Speaking fees from MerckSerono, Advisory board for MerckSerono and Biogen
Anna Karin Hedström: nothing to disclose
Louis Flamand: nothing to disclose
Masaru Ihira: nothing to disclose
Tetsushi Yoshikawa: nothing to disclose
Oluf Andersen: nothing to disclose
Jan Hillert: received honoraria for serving on advisory boards for Biogen, Sanofi-Genzyme and Novartis and speaker's fees from Biogen, Novartis, Merck-Serono, Bayer-Schering, Teva and Sanofi-Genzyme. He has served as P.I. for projects, or received unrestricted research support from, BiogenIdec, Merck, Novartis and Sanofi-Genzyme.
Lars Alfredsson: nothing to disclose
Tim Waterboer: nothing to disclose
Peter Sundström: nothing to disclose
Tomas Olsson has received lecture and/or Advisory board honoraria, and unrestricted MS research grants from Biogen, Novartis, Sanofi, Merck and Roche
Ingrid Kockum: nothing to disclose
Anna Fogdell-Hahn: nothing to disclose

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