Epstein–Barr virus shapes intrathecal Th1/Th17 immunity and parenchymal involvement in neuro-Behçet’s disease
8 affiliations
- 1"Transmission, Control and Immunobiology of Infections" Laboratory, Institut Pasteur de Tunis, Tunis, Tunisia.
- 2Faculty of Sciences of Tunis, Tunis El Manar University, Tunis, Tunisia.
- 3Neurology Department, Mongi Ben Hmida National Institute of Neurology, Tunis, Tunisia.
- 4Faculty of Medicine, Tunis El Manar University, Tunis, Tunisia.
- 5Department of Experimental and Clinical Medicine (DMSC), University of Florence, Florence, Italy.
- 6Department of Physiology, Morehouse School of Medicine, Atlanta, GA, United States.
- 7"Virus, Vectors and Hosts" Laboratory, Institut Pasteur de Tunis, Tunis, Tunisia.
- 8Department of Microbiology, Immunology and Infectious Diseases, College of Medicine and Health Science, Manama, Bahrain.
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.
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BibTeX
@article{laamari2026epsteinbarr,
title = {{Epstein–Barr virus shapes intrathecal Th1/Th17 immunity and parenchymal involvement in neuro-Behçet’s disease}},
author = {Rafika Ben Laamari and Zakaria Saied and Olfa Maghrebi and Khadija Bahrini and Jihène Bekir and Amani Stiti and Adel Driss and Dorra Rezig and Mohamed Ridha Barbouche and Samia Ben Sassi and Meriam Belghith},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1921667},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1921667/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Epstein–Barr virus shapes intrathecal Th1/Th17 immunity and parenchymal involvement in neuro-Behçet’s disease
AU - Rafika Ben Laamari
AU - Zakaria Saied
AU - Olfa Maghrebi
AU - Khadija Bahrini
AU - Jihène Bekir
AU - Amani Stiti
AU - Adel Driss
AU - Dorra Rezig
AU - Mohamed Ridha Barbouche
AU - Samia Ben Sassi
AU - Meriam Belghith
PY - 2026
DA - 2026/10/08
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1921667
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1921667/full
AB - 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.
SN - 1664-3224
ER -