RESEARCHERS have identified a promising blood-based biomarker that could help distinguish multiple sclerosis (MS) from other inflammatory neurological disorders, according to a new multicentre study.
Differentiating MS from myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and neuromyelitis optica spectrum disorder (NMOSD) remains a persistent clinical challenge, particularly in patients who test negative for established disease-specific antibodies. Overlapping symptoms and imaging findings often complicate diagnosis, delaying appropriate treatment.
In this retrospective, longitudinal case-control study, investigators analysed plasma samples from 2,091 patients with neuroinflammatory diseases and 1,976 healthy controls across cohorts in Austria, Germany, and the United States. The study focused on levels of immunoglobulin G antibodies targeting Epstein-Barr virus (EBV), specifically Epstein-Barr nuclear antigen 1 (EBNA-1) peptides, measured at diagnosis and across three follow-up time points over two years.
Persistent EBNA-1 Antibody Levels Strongly Linked to MS
The findings showed a striking difference between MS and other conditions. In the test cohort, 96.2% of patients with MS exhibited persistently high EBNA-1 antibody titres in at least two of four measurements. In contrast, this pattern was observed in only 7.7% of patients with MOGAD and 18.0% with NMOSD. Similar results were confirmed in the validation cohort, where over 95% of patients with MS showed sustained high titres, compared with fewer than 18% in the other groups.
Importantly, even among patients with NMOSD who were negative for aquaporin-4 antibodies-a subgroup that is particularly difficult to diagnose-persistent high EBNA-1 titres were rare, further supporting the specificity of this marker for MS.
The authors suggest that longitudinal measurement of EBNA-1–specific antibodies could serve as a valuable adjunct diagnostic tool, especially in ambiguous or seronegative cases. Rather than relying on a single measurement, repeated testing over time appears critical to improving diagnostic accuracy.
Findings Strengthen Evidence Connecting Epstein–Barr Virus to MS
While further prospective validation is needed, these findings strengthen the growing body of evidence linking EBV to MS and highlight a potential pathway for improving early and accurate differentiation between neuroinflammatory diseases.
Reference
Vietzen H et al. Epstein-Barr Virus Antibodies to Differentiate Multiple Sclerosis From Other Neuroinflammatory Diseases. JAMA Neurol.2026; doi: 10.1001/jamaneurol.2026.0240
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