Early identification of individuals at risk for multiple sclerosis by quantification of EBNA-1381-452-specific antibody titers

Abstract Multiple sclerosis (MS) is an immune-mediated demyelinating disease. Epstein-Barr virus (EBV) encodes for the EBNA-1381-452 region that induces autoreactive antibody responses, which are likely critically involved in MS pathogenesis. Here we investigate whether these EBNA-1381-452-specific...

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Main Authors: Hannes Vietzen, Laura M. Kühner, Sarah M. Berger, Markus Ponleitner, Marianne Graninger, Charlotte Pistorius, Christof Jungbauer, Markus Reindl, Henrieke Saucke, Franziska Kauth, Eva-Maria Wendel, Kevin Rostásy, Markus Breu, Barbara Kornek, Gabriel Bsteh, Thomas Berger, Paulus Rommer, Elisabeth Puchhammer-Stöckl
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-61751-9
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author Hannes Vietzen
Laura M. Kühner
Sarah M. Berger
Markus Ponleitner
Marianne Graninger
Charlotte Pistorius
Christof Jungbauer
Markus Reindl
Henrieke Saucke
Franziska Kauth
Eva-Maria Wendel
Kevin Rostásy
Markus Breu
Barbara Kornek
Gabriel Bsteh
Thomas Berger
Paulus Rommer
Elisabeth Puchhammer-Stöckl
author_facet Hannes Vietzen
Laura M. Kühner
Sarah M. Berger
Markus Ponleitner
Marianne Graninger
Charlotte Pistorius
Christof Jungbauer
Markus Reindl
Henrieke Saucke
Franziska Kauth
Eva-Maria Wendel
Kevin Rostásy
Markus Breu
Barbara Kornek
Gabriel Bsteh
Thomas Berger
Paulus Rommer
Elisabeth Puchhammer-Stöckl
author_sort Hannes Vietzen
collection DOAJ
description Abstract Multiple sclerosis (MS) is an immune-mediated demyelinating disease. Epstein-Barr virus (EBV) encodes for the EBNA-1381-452 region that induces autoreactive antibody responses, which are likely critically involved in MS pathogenesis. Here we investigate whether these EBNA-1381-452-specific antibodies can serve as a biomarker to identify at-risk individuals for MS. We quantify EBNA-1381-452-specific antibody titers from 324 relapsing-remitting MS patients and 324 matched controls in longitudinal follow-up plasma samples, starting from the individual’s EBV-seroconversion. In MS patients, significantly elevated EBNA-1381-452-specific IgG titers are identified that are increased already as early as nine months after EBV-seroconversion (OR:5.7; 95% CI: 4.1-8.1; P < 0.0001) and a median 5.4 years prior to MS diagnosis. Especially, the presence of continuously high EBNA-1381-452-specific antibody titers is associated with a more rapid MS diagnosis after EBV-seroconversion (P < 0.0001). Thus, the quantification of EBNA-1381-452-specific IgG antibody levels may provide a prognostic biomarker to determine the individual’s risk for the diagnosis of MS.
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spelling doaj-art-90b79b7607034daea9b8d82dc8d16b5d2025-08-20T04:03:01ZengNature PortfolioNature Communications2041-17232025-07-0116111110.1038/s41467-025-61751-9Early identification of individuals at risk for multiple sclerosis by quantification of EBNA-1381-452-specific antibody titersHannes Vietzen0Laura M. Kühner1Sarah M. Berger2Markus Ponleitner3Marianne Graninger4Charlotte Pistorius5Christof Jungbauer6Markus Reindl7Henrieke Saucke8Franziska Kauth9Eva-Maria Wendel10Kevin Rostásy11Markus Breu12Barbara Kornek13Gabriel Bsteh14Thomas Berger15Paulus Rommer16Elisabeth Puchhammer-Stöckl17Center for Virology, Medical University of ViennaCenter for Virology, Medical University of ViennaCenter for Virology, Medical University of ViennaDepartment of Neurology, Medical University of ViennaCenter for Virology, Medical University of ViennaAustrian Red Cross, Blood Service for Vienna, Lower Austria and BurgenlandAustrian Red Cross, Blood Service for Vienna, Lower Austria and BurgenlandClinical Department of Neurology, Medical University of InnsbruckDepartment of Pediatric Neurology, Children´s Hospital Datteln, University Witten/ HerdeckeDepartment of Pediatric Neurology, Children´s Hospital Datteln, University Witten/ HerdeckeDivision of Pediatric Neurology, Department of Pediatrics, OlgahospitalDepartment of Pediatric Neurology, Children´s Hospital Datteln, University Witten/ HerdeckeDepartment of Neurology, Medical University of ViennaDepartment of Neurology, Medical University of ViennaDepartment of Neurology, Medical University of ViennaDepartment of Neurology, Medical University of ViennaDepartment of Neurology, Medical University of ViennaCenter for Virology, Medical University of ViennaAbstract Multiple sclerosis (MS) is an immune-mediated demyelinating disease. Epstein-Barr virus (EBV) encodes for the EBNA-1381-452 region that induces autoreactive antibody responses, which are likely critically involved in MS pathogenesis. Here we investigate whether these EBNA-1381-452-specific antibodies can serve as a biomarker to identify at-risk individuals for MS. We quantify EBNA-1381-452-specific antibody titers from 324 relapsing-remitting MS patients and 324 matched controls in longitudinal follow-up plasma samples, starting from the individual’s EBV-seroconversion. In MS patients, significantly elevated EBNA-1381-452-specific IgG titers are identified that are increased already as early as nine months after EBV-seroconversion (OR:5.7; 95% CI: 4.1-8.1; P < 0.0001) and a median 5.4 years prior to MS diagnosis. Especially, the presence of continuously high EBNA-1381-452-specific antibody titers is associated with a more rapid MS diagnosis after EBV-seroconversion (P < 0.0001). Thus, the quantification of EBNA-1381-452-specific IgG antibody levels may provide a prognostic biomarker to determine the individual’s risk for the diagnosis of MS.https://doi.org/10.1038/s41467-025-61751-9
spellingShingle Hannes Vietzen
Laura M. Kühner
Sarah M. Berger
Markus Ponleitner
Marianne Graninger
Charlotte Pistorius
Christof Jungbauer
Markus Reindl
Henrieke Saucke
Franziska Kauth
Eva-Maria Wendel
Kevin Rostásy
Markus Breu
Barbara Kornek
Gabriel Bsteh
Thomas Berger
Paulus Rommer
Elisabeth Puchhammer-Stöckl
Early identification of individuals at risk for multiple sclerosis by quantification of EBNA-1381-452-specific antibody titers
Nature Communications
title Early identification of individuals at risk for multiple sclerosis by quantification of EBNA-1381-452-specific antibody titers
title_full Early identification of individuals at risk for multiple sclerosis by quantification of EBNA-1381-452-specific antibody titers
title_fullStr Early identification of individuals at risk for multiple sclerosis by quantification of EBNA-1381-452-specific antibody titers
title_full_unstemmed Early identification of individuals at risk for multiple sclerosis by quantification of EBNA-1381-452-specific antibody titers
title_short Early identification of individuals at risk for multiple sclerosis by quantification of EBNA-1381-452-specific antibody titers
title_sort early identification of individuals at risk for multiple sclerosis by quantification of ebna 1381 452 specific antibody titers
url https://doi.org/10.1038/s41467-025-61751-9
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