Dejan Jakimovski1, Murali Ramanathan2, Bianca Weinstock-Guttman3, Niels Bergsland1, Deepa P Ramasamay1, Ellen Carl1, Michael G Dwyer1, Robert Zivadinov4. 1. Buffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, NY, USA. 2. Department of Pharmaceutical Sciences, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, NY, USA. 3. Jacobs Multiple Sclerosis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, NY, USA. 4. Buffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, NY, USA/ Center for Biomedical Imaging, Clinical and Translational Science Institute, University at Buffalo, The State University of New York, Buffalo, NY, USA.
Abstract
BACKGROUND: Epstein-Barr virus (EBV) infection has been associated with higher clinical activity and risk of multiple sclerosis (MS). OBJECTIVE: To evaluate associations between EBV-specific humoral response and magnetization transfer ratio (MTR)-derived measure in MS patients and healthy controls (HCs). METHODS: The study included 101 MS patients (69 relapsing-remitting multiple sclerosis (RRMS) and 32 secondary-progressive multiple sclerosis (SPMS)) and 41 HCs who underwent clinical, serological, and magnetic resonance imaging (MRI) investigations. MTR values of T1 or T2 lesion volume (LV), normal-appearing (NA) brain tissue (NABT), gray matter (NAGM), and white matter (NAWM) were obtained. Enzyme-linked immunosorbent assay was used to quantify EBV antibody levels. Partial correlations corrected for MRI strength were used, and Benjamini-Hochberg-adjusted p-values < 0.05 were considered significant. RESULTS: MS patients had significantly higher anti-EBV nuclear antigen-1 (EBNA-1) titer when compared to HCs (107.9 U/mL vs 27.8 U/mL, p < 0.001). Within the MS group, higher serum anti-EBNA-1 titer was significantly correlated with lower T1-LV MTR (r = -0.287, p = 0.035). Within the RRMS group, higher serum anti-EBNA-1 titer was associated with T1-LV MTR (r = -0.524, p = 0.001) and NAGM MTR (r = -0.308, p = 0.043). These associations were not present in HCs or SPMS patients. CONCLUSION: Greater EBV humoral response is associated with lower GM MTR changes and focal destructive lesion pathology in RRMS patients.
BACKGROUND:Epstein-Barr virus (EBV) infection has been associated with higher clinical activity and risk of multiple sclerosis (MS). OBJECTIVE: To evaluate associations between EBV-specific humoral response and magnetization transfer ratio (MTR)-derived measure in MS patients and healthy controls (HCs). METHODS: The study included 101 MS patients (69 relapsing-remitting multiple sclerosis (RRMS) and 32 secondary-progressive multiple sclerosis (SPMS)) and 41 HCs who underwent clinical, serological, and magnetic resonance imaging (MRI) investigations. MTR values of T1 or T2 lesion volume (LV), normal-appearing (NA) brain tissue (NABT), gray matter (NAGM), and white matter (NAWM) were obtained. Enzyme-linked immunosorbent assay was used to quantify EBV antibody levels. Partial correlations corrected for MRI strength were used, and Benjamini-Hochberg-adjusted p-values < 0.05 were considered significant. RESULTS: MS patients had significantly higher anti-EBV nuclear antigen-1 (EBNA-1) titer when compared to HCs (107.9 U/mL vs 27.8 U/mL, p < 0.001). Within the MS group, higher serum anti-EBNA-1 titer was significantly correlated with lower T1-LV MTR (r = -0.287, p = 0.035). Within the RRMS group, higher serum anti-EBNA-1 titer was associated with T1-LV MTR (r = -0.524, p = 0.001) and NAGMMTR (r = -0.308, p = 0.043). These associations were not present in HCs or SPMS patients. CONCLUSION: Greater EBV humoral response is associated with lower GMMTR changes and focal destructive lesion pathology in RRMS patients.
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