Virus-specific effects of disease-modifying therapies on herpesvirus antibody titers in multiple sclerosis
Abstract
Epstein-Barr virus (EBV) and human herpesvirus 6 (HHV-6) have both been implicated in multiple sclerosis (MS), yet it remains unclear whether disease-modifying therapies (DMTs) shape antiviral humoral responses. We analyzed antiviral IgG titers in MS patients stratified by current DMT (N = 498 for HHV-6A/B, 410 for EBNA-1, 361 for cytomegalovirus (CMV)). Multivariable regression models were built separately for each virus, adjusting for age, sex, HLA-DRB1*15:01 carriage, EDSS, treatment duration, and prior treatment efficacy, using interferon-beta (IFN-beta) as the reference category. The HHV-6A/B model showed a significant global fit (p = 1.16 × 10^-6), with fingolimod independently associated with reduced titers relative to IFN-beta (p = 0.006), alongside negative effects of age (p = 0.001) and higher titers among HLA-DRB1*15:01 carriers (p = 0.028). Neither the EBNA-1 nor the CMV model reached global significance, although age remained a strong predictor of CMV IgG (p = 0.002). These findings indicate that DMTs do not exert a uniform effect on herpesvirus serology in MS: fingolimod is specifically associated with attenuated HHV-6A/B seroreactivity, whereas EBNA-1 and CMV titers appear to be governed mainly by host factors. Interpreting antiviral serology in MS from a treatment-stratified perspective may therefore be necessary to identify biologically significant signals specific to each drug.
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BibTeX
@article{ruberto2026virusspecific,
title = {{Virus-specific effects of disease-modifying therapies on herpesvirus antibody titers in multiple sclerosis}},
author = {Stefano Ruberto and María I. Domínguez-Mozo and Luisa María Villar and Lucienne Costa-Frossard and Noelia Villarrubia and Yolanda Aladro and Ignacio Casanova-Peño and María Luisa Martínez-Ginés and José Manuel García-Domínguez and Isabel Ortega-Madueño and Guadalupe Pérez de Villar and Andrea Alonso-Garrido and Iván Pérez-Gutiérrez and María A. García-Martínez and Rafael Arroyo and Roberto Álvarez-Lafuente},
journal = {Scientific Reports},
year = {2026},
month = oct,
doi = {10.1038/s41598-026-73983-w},
url = {https://www.nature.com/articles/s41598-026-73983-w},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Virus-specific effects of disease-modifying therapies on herpesvirus antibody titers in multiple sclerosis
AU - Stefano Ruberto
AU - María I. Domínguez-Mozo
AU - Luisa María Villar
AU - Lucienne Costa-Frossard
AU - Noelia Villarrubia
AU - Yolanda Aladro
AU - Ignacio Casanova-Peño
AU - María Luisa Martínez-Ginés
AU - José Manuel García-Domínguez
AU - Isabel Ortega-Madueño
AU - Guadalupe Pérez de Villar
AU - Andrea Alonso-Garrido
AU - Iván Pérez-Gutiérrez
AU - María A. García-Martínez
AU - Rafael Arroyo
AU - Roberto Álvarez-Lafuente
PY - 2026
DA - 2026/10/05
JO - Scientific Reports
DO - 10.1038/s41598-026-73983-w
UR - https://www.nature.com/articles/s41598-026-73983-w
AB - Epstein-Barr virus (EBV) and human herpesvirus 6 (HHV-6) have both been implicated in multiple sclerosis (MS), yet it remains unclear whether disease-modifying therapies (DMTs) shape antiviral humoral responses. We analyzed antiviral IgG titers in MS patients stratified by current DMT (N = 498 for HHV-6A/B, 410 for EBNA-1, 361 for cytomegalovirus (CMV)). Multivariable regression models were built separately for each virus, adjusting for age, sex, HLA-DRB1*15:01 carriage, EDSS, treatment duration, and prior treatment efficacy, using interferon-beta (IFN-beta) as the reference category. The HHV-6A/B model showed a significant global fit (p = 1.16 × 10^-6), with fingolimod independently associated with reduced titers relative to IFN-beta (p = 0.006), alongside negative effects of age (p = 0.001) and higher titers among HLA-DRB1*15:01 carriers (p = 0.028). Neither the EBNA-1 nor the CMV model reached global significance, although age remained a strong predictor of CMV IgG (p = 0.002). These findings indicate that DMTs do not exert a uniform effect on herpesvirus serology in MS: fingolimod is specifically associated with attenuated HHV-6A/B seroreactivity, whereas EBNA-1 and CMV titers appear to be governed mainly by host factors. Interpreting antiviral serology in MS from a treatment-stratified perspective may therefore be necessary to identify biologically significant signals specific to each drug.
SN - 2045-2322
ER -