Robert Zivadinov1, Murali Ramanathan2, Jesper Hagemeier3, Niels Bergsland3, Deepa P Ramasamy3, Jacqueline Durfee3, Channa Kolb4, Bianca Weinstock-Guttman4. 1. Buffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, United States; Center for Biomedical Imaging at Clinical Translational Science Institute, University at Buffalo, State University of New York, Buffalo, NY, United States. Electronic address: rzivadinov@bnac.net. 2. Department of Pharmaceutical Sciences, State University of New York, Buffalo, NY, United States. 3. Buffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, United States. 4. Jacobs Multiple Sclerosis Center, Department of Neurology, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, United States.
Abstract
BACKGROUND: Teriflunomide has been shown to slow cortical gray matter (GM) atrophy in patients with multiple sclerosis (MS). Previous work showed that higher levels of Epstein-Barr virus (EBV) are associated with greater development of cortical pathology in MS. OBJECTIVES: To investigate whether the effect of teriflunomide on cortical volume loss in relapsing MS patients may be associated with the change in humoral response to EBV. METHODS: This was a prospective, observational, single-blinded, longitudinal study of 30 relapsing MS patients, who started treatment with teriflunomide, and 20 age- and sex-matched healthy controls (HCs). Subjects were assessed at baseline, 6 and 12 months with clinical, MRI and EBV examinations. MRI outcomes included percent changes in cortical, GM, deep GM and whole brain volumes. Serum samples were analyzed for IgG antibodies titers against EBV viral capsid antigen (VCA) and nuclear antigen-1 (EBNA-1). RESULTS: There were no significant differences in anti-VCA and anti-EBNA-1 IgG titers between MS patients and HC at baseline. However, over the 12-month follow-up, MS patients experienced a greater decrease in anti-EBNA-1 (-35.1, p = .003) and anti-VCA (-15.9, p = .05) IgG titers, whereas no significant changes were observed in HCs (-3.7 and -1.6, respectively). MS patients who showed the highest decrease in anti-EBV VCA and EBNA-1 IgG titers from baseline to follow-up, developed less cortical (p < .001 and p = .02) and GM volume loss (p = .004 for both), respectively. CONCLUSIONS: Teriflunomide's effect on slowing cortical and GM volume loss may be mediated by its effect on altering humoral response to EBV.
BACKGROUND:Teriflunomide has been shown to slow cortical gray matter (GM) atrophy in patients with multiple sclerosis (MS). Previous work showed that higher levels of Epstein-Barr virus (EBV) are associated with greater development of cortical pathology in MS. OBJECTIVES: To investigate whether the effect of teriflunomide on cortical volume loss in relapsing MSpatients may be associated with the change in humoral response to EBV. METHODS: This was a prospective, observational, single-blinded, longitudinal study of 30 relapsing MSpatients, who started treatment with teriflunomide, and 20 age- and sex-matched healthy controls (HCs). Subjects were assessed at baseline, 6 and 12 months with clinical, MRI and EBV examinations. MRI outcomes included percent changes in cortical, GM, deep GM and whole brain volumes. Serum samples were analyzed for IgG antibodies titers against EBV viral capsid antigen (VCA) and nuclear antigen-1 (EBNA-1). RESULTS: There were no significant differences in anti-VCA and anti-EBNA-1 IgG titers between MSpatients and HC at baseline. However, over the 12-month follow-up, MSpatients experienced a greater decrease in anti-EBNA-1 (-35.1, p = .003) and anti-VCA (-15.9, p = .05) IgG titers, whereas no significant changes were observed in HCs (-3.7 and -1.6, respectively). MSpatients who showed the highest decrease in anti-EBV VCA and EBNA-1 IgG titers from baseline to follow-up, developed less cortical (p < .001 and p = .02) and GM volume loss (p = .004 for both), respectively. CONCLUSIONS:Teriflunomide's effect on slowing cortical and GM volume loss may be mediated by its effect on altering humoral response to EBV.
Authors: Amit Bar-Or; Michael P Pender; Rajiv Khanna; Lawrence Steinman; Hans-Peter Hartung; Tap Maniar; Ed Croze; Blake T Aftab; Gavin Giovannoni; Manher A Joshi Journal: Trends Mol Med Date: 2019-12-17 Impact factor: 11.951