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Author Spotlight: Novel Assay for Studying B-Cell Responses in Multiple Sclerosis Research
Published on: December 1, 2023
Humoral response to EBV is associated with cortical atrophy and lesion burden in patients with MS
Robert Zivadinov1, Nicole Cerza1, Jesper Hagemeier1
1Buffalo Neuroimaging Analysis Center (R.Z., D.B., M.R.) and Jacobs Multiple Sclerosis Center (B.W.-G.), Department of Neurology; MR Imaging Clinical Translational Research Center (R.Z., N.C., J.H., E.C., D.P.R., M.R.), School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY; and Department of Pharmaceutical Sciences (M.R.), State University of New York, Buffalo, NY.
Objective:
Because dysregulated Epstein-Barr virus (EBV)-infected B cells may induce meningeal inflammation, which contributes to cortical pathology in multiple sclerosis (MS), we investigated associations between antibody responses to EBV and development of cortical pathology in MS.
Methods:
We included 539 patients with MS (369 with relapsing-remitting MS, 135 with secondary progressive MS, and 35 with primary progressive MS), 66 patients with clinically isolated syndrome (CIS), 63 patients with other neurologic diseases (OND), and 178 age- and sex-matched healthy controls (HC). All participants were scanned on 3T MRI. Serum samples were analyzed for IgG antibodies against EBV viral capsid antigen (VCA) and EBV nuclear antigen-1 (EBNA-1), and their quartiles were determined on the whole study sample. Differences between the study groups were assessed using analysis of covariance adjusted for multiple comparisons.
Results:
More than 30% of patients with MS and CIS presented with the highest quartile of anti-EBV-VCA and -EBNA-1 status compared to ≤10% of HC (p < 0.001). The figures were 9 (14.3%) and 7 (12.3%) for patients with OND. Patients with MS with the highest quartile of anti-EBV-VCA showed significantly increased T2 lesion volume (p = 0.001), T1 lesion number (p = 0.002), and T1 lesion volume (p = 0.04) and decreased gray matter (p = 0.041) and cortical (p = 0.043) volumes compared to patients with MS with lower quartiles. No significant differences of MRI outcomes in patients with CIS, patients with OND, and HC with lower or highest quartiles of anti-EBV-VCA and -EBNA-1 were detected.
Conclusions:
Humoral response to anti-EBV-VCA and -EBNA-1 is associated with more advanced cortical atrophy, accumulation of chronic T1 black holes, and focal white matter lesions in patients with MS.
Insights
High antibody responses to Epstein-Barr virus (EBV) are linked to greater cortical atrophy and brain lesions in multiple sclerosis (MS) patients. This suggests EBV
Area of Science:
- Neuroimmunology
- Viral Immunology
- Neuroimaging
Background:
- Dysregulated Epstein-Barr virus (EBV) infected B cells may cause meningeal inflammation, contributing to cortical pathology in multiple sclerosis (MS).
- Investigating the link between EBV antibody responses and MS cortical pathology is crucial for understanding disease mechanisms.
Purpose of the Study:
- To examine the association between antibody responses to Epstein-Barr virus (EBV) and the development of cortical pathology in patients with multiple sclerosis (MS).
- To compare EBV antibody levels and MRI-derived brain pathology metrics across MS subtypes, clinically isolated syndrome (CIS), other neurologic diseases (OND), and healthy controls (HC).
Main Methods:
- Serum IgG antibodies against EBV viral capsid antigen (VCA) and EBV nuclear antigen-1 (EBNA-1) were measured in 539 MS patients, 66 CIS patients, 63 OND patients, and 178 HC.
- Participants underwent 3T MRI scans. Antibody levels were categorized into quartiles.
- Analysis of covariance was used to assess differences in MRI outcomes (lesion volume, gray matter, cortical volume) based on EBV antibody quartiles.
Main Results:
- Over 30% of MS and CIS patients exhibited the highest quartile of anti-EBV-VCA and anti-EBNA-1 antibodies, compared to less than 10% of HC.
- In MS patients, the highest quartile of anti-EBV-VCA was significantly associated with increased T2 lesion volume, T1 lesion number, and T1 lesion volume.
- Higher anti-EBV-VCA antibody levels correlated with decreased gray matter and cortical volumes in MS patients. No significant MRI differences were found in CIS, OND, or HC groups.
Conclusions:
- Humoral immune response to EBV (anti-EBV-VCA and anti-EBNA-1) is associated with more advanced cortical atrophy in MS patients.
- Elevated EBV antibody responses correlate with increased accumulation of chronic T1 black holes and focal white matter lesions in MS.
- These findings highlight a potential role for EBV in driving MS neuropathology, particularly cortical damage.
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