Multiple sclerosis-associated EBNA2 variants influence the response to peginterferon beta-1a therapy
Year: 2026
Type: article
Abstract: BACKGROUND: Strong evidence links Epstein-Barr virus (EBV) infection to Multiple Sclerosis (MS). Peginterferon beta-1a (peg-IFN), currently the most used interferon formulation among first-line treatments in MS, displays immunomodulatory, anti-inflammatory, and antiviral properties and remains also an important therapeutic option in conditions such as pregnancy, lactation and aging patients. OBJECTIVES: In this study we evaluated the ability of peg-IFN to restore a homeostatic EBV-host interaction in MS by regulating antiviral and immunometabolic responses. METHODS: In people with MS (pwMS), peripheral blood mononuclear cells (PBMCs) were analyzed before (T0) and after six months (T6mos) of peg-IFN administration: IFN-stimulated gene (ISG) levels, EBV DNA load, Epstein-Barr nuclear antigen 2 (EBNA2) allele distribution, and T-lymphocyte phenotyping with glycolytic metabolism were assessed. RESULTS: T lymphocytes, and reduced EBV DNA load without altering EBNA2 allele distribution. Notably, ISG expression increase at T6mos in pwMS infected by the non-risk 1.3B EBNA2 allele, correlating with a better long-term response to peg-IFN after 2-years. Lower T-cell glycolytic capacity at T0 predicted higher peg-IFN responsiveness in pwMS carrying the 1.3B allele, suggesting that EBNA2 variants might be predictive of response to peg-IFN. CONCLUSION: Here, we found that infection with MS-associated EBNA2 variants might be involved in the clinical response to peg-IFN therapy. The predictive model developed, which integrates immunological and viral parameters, may help clinicians in a finer selection of first-line therapies tailored to patient profiles, supporting personalized medicine approaches.
Source: Journal of Autoimmunity
Authors: Caterina Veroni, Fortunata Carbone, Daniela Ricci, Stefania Proietti, Silvia Romano, Maria Chiara Buscarinu, Fabiana Rizzo, Antonio Marrone, Teresa Micillo, Francesco Perna, Federica Garziano, Gisella Guerrera, Paola Valentino, Chiara Meloni, Gianmarco Bellucci, Antonio Bertolotto, Luca Battistini, Giovanni Ristori, Diego Centonze, Giuseppe Matarese, Eliana M. Coccia, Marco Salvetti, Martina Severa, Rosella Mechelli
Institutions: Istituto Superiore di Sanità, Fondazione Santa Lucia, National Research Council, Istituti di Ricovero e Cura a Carattere Scientifico, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele, Sapienza University of Rome, Azienda Ospedaliera Universitaria Università degli Studi della Campania Luigi Vanvitelli, Federico II University Hospital, University of Naples Federico II, Ospedale Monaldi, Ospedale San Luigi Gonzaga, Neuroscience Institute Cavalieri Ottolenghi, Ospedale Koelliker, University of Rome Tor Vergata, Istituto Neurologico Mediterraneo, San Raffaele University of Rome
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $5,420
OpenAlex ID: W7128675701