Work

Epstein–Barr virus shapes intrathecal Th1/Th17 immunity and parenchymal involvement in neuro-Behçet’s disease

Year: 2026

Type: article

Abstract: Introduction: Human herpesviruses (HHVs) are implicated in neuro-inflammatory diseases due to their ability to establish persistent latency and reactivate in the context of immune dysregulation. Whilst Epstein -Barr virus (EBV) is recognized as a key factor in multiple sclerosis (MS), its role in neuro-Behçet's disease (NBD) remains poorly understood. Methods: Serum and paired CSF samples were obtained from treatment-naïve patients with NBD and MS. Neurotropic viral DNA in CSF was screened by multiplex PCR. Virus-specific IgG antibodies against HSV-1 and EBV antigens (VCA and EBNA1) were measured by ELISA in serum and CSF. Real-time PCR was used to assess the expression of EBV latent genes (LMP1 and EBNA1), as well as cytokines and transcription factors, in CSF samples from NBD patients. Results: In this study, we demonstrate a high prevalence of EBV DNA in the cerebrospinal fluid (CSF) of patients with NBD (71.43%), significantly higher than that observed in MS (35.29%), whereas other neurotropic herpesviruses are rarely detected. Notably, the presence of EBV in the CSF is not associated with a specific intrathecal humoral response, suggesting predominantly latent viral persistence and cell-mediated immune control. The concurrent expression of the latent proteins LMP1 and EBNA1 indicates a type II latency program, capable of activating interferon pathways. EBV-positive patients exhibit an immune signature characterized by significantly elevated levels of IFN-γ and IFN-α, associated with Th1/Th17 polarization and reduced FOXP3 expression, reflecting a Th17/Treg imbalance. Furthermore, EBV status is associated with distinct clinical phenotypes, with parenchymal forms being observed exclusively in EBV-positive patients. Conclusion: This suggests that EBV may contribute to the pathophysiology of NBD by promoting a pro-inflammatory intrathecal microenvironment. It also positions EBV as a potential biomarker and therapeutic target in this condition.

Source: Frontiers in Immunology

DOI: 10.3389/fimmu.2026.1921667