How EBV Antibodies Might Help Differentiate Multiple Sclerosis From MOGAD and NMOSD: Tanuja Chitnis, MD

WATCH TIME: 4 minutes

“If a patient presents with a syndrome suggestive of multiple sclerosis and they are not EBNA-1 positive, that gives me pause. It does not rule out MS, but it pushes me to think more carefully about alternative diagnoses.”

The role of Epstein-Barr virus (EBV) in multiple sclerosis (MS) has become increasingly central, particularly following large epidemiologic studies suggesting EBV infection is a near-universal antecedent to MS development.¹ While this has strengthened the case for EBV as a key environmental factor, translating these findings into clinically useful biomarkers remains challenging, especially when distinguishing MS from related neuroinflammatory conditions such as myelin oligodendrocyte glycoprotein antibody–associated disease (MOGAD) and neuromyelitis optica spectrum disorder (NMOSD).

In a recent multicenter case-control study published in JAMA Neurology, investigators evaluated EBV-specific antibody responses across a large cohort of patients with neuroinflammatory disease and healthy controls. The analysis included more than 2000 patients and nearly 2000 controls, with a focus on Epstein-Barr nuclear antigen 1 (EBNA-1) immunoglobulin G titers. Results showed that high EBNA-1 antibody titers were more frequent and more persistently elevated in patients with MS compared with those with MOGAD or NMOSD, suggesting potential utility as a differentiating biomarker.

Although EBNA-1 antibodies were detected across multiple disease groups, their prevalence and persistence were notably higher in MS. Nearly all patients with MS demonstrated EBNA-1 positivity, whereas lower and more variable rates were observed in MOGAD, NMOSD, and other neurologic diseases. These findings support the concept that serial EBV-specific antibody measurement may serve as a complementary biomarker in cases where diagnostic uncertainty remains.

Following publication of the study, Tanuja Chitnis, MD, division chief of neuroimmunology at Brigham and Women’s Hospital, spoke with NeurologyLive® about the clinical implications of these findings. In the discussion, she explains how EBV antibody profiles may aid in differentiating MS from related disorders, where these measures fit within the broader biomarker landscape, and how future research may further refine EBV-based diagnostics.

REFERENCES
1. Bjornevik K, Cortese M, Healy BC, et al. Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis. Science. 2022;375(6578):296-301. doi:10.1126/science.abj8222
2. Vietzen H, Kuhner LM, Berger SM, et al. Epstein-Barr Virus Antibodies to Differentiate Multiple Sclerosis From Other Neuroinflammatory Diseases. JAMA Neurol. Published online March 9, 2026. doi:10.1001/jamaneurol.2026.0240