Early identification of individuals at risk for multiple sclerosis by quantification of EBNA-1381-452-specific antibody titers
Multiple sclerosis (MS) is an immune-mediated demyelinating disease. Epstein-Barr virus (EBV) encodes for the EBNA-1<sub>381-452</sub> region that induces autoreactive antibody responses, which are likely critically involved in MS pathogenesis. Here we investigate whether these EBNA-1<sub>381-452</sub>-specific antibodies can serve as a biomarker to identify at-risk individuals for MS. We quantify EBNA-1<sub>381-452</sub>-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-1<sub>381-452</sub>-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-1<sub>381-452</sub>-specific antibody titers is associated with a more rapid MS diagnosis after EBV-seroconversion (P < 0.0001). Thus, the quantification of EBNA-1<sub>381-452</sub>-specific IgG antibody levels may provide a prognostic biomarker to determine the individual's risk for the diagnosis of MS.
Authors
- Markus Breu (ORCID: https://orcid.org/0000-0003-3825-5749)
- Christof Jungbauer (ORCID: https://orcid.org/0000-0002-2482-7147)
- Barbara Kornek (ORCID: https://orcid.org/0000-0002-1851-6967)
- Paulus Stefan Rommer (ORCID: https://orcid.org/0000-0001-5209-6647)
- Gabriel Bsteh (ORCID: https://orcid.org/0000-0002-0825-0851)
- Hannes Vietzen (ORCID: https://orcid.org/0000-0003-3993-6538)
- S. Berger (ORCID: https://orcid.org/0000-0003-4633-8245)
- Markus Ponleitner (ORCID: https://orcid.org/0000-0002-3709-1845)
- Kevin M. Rostasy (ORCID: https://orcid.org/0000-0002-2180-5321)
- Thomas Berger (ORCID: https://orcid.org/0000-0001-5626-1144)
- Markus Reindl (ORCID: https://orcid.org/0000-0003-2817-1402)
- Eva‐Maria Wendel (ORCID: https://orcid.org/0000-0002-5242-1830)
- Marianne Graninger (ORCID: https://orcid.org/0000-0002-2152-7798)
- Laura M. Kühner (ORCID: https://orcid.org/0009-0000-5830-9009)
- Elisabeth Puchhammer-Stöckl
- Charlotte Pistorius
- Henrieke Saucke
- Franziska Kauth (ORCID: https://orcid.org/0009-0005-8307-5829)
Institutions
- Innsbruck Medical University (AT)
- Witten/Herdecke University (DE)
- Universität Innsbruck (AT)
- Paracelsus Medical University (AT)
- Olgahospital (DE)
- Austrian Red Cross (AT)
- Medical University of Vienna (AT)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-07-14
- DOI
- https://doi.org/10.1038/s41467-025-61751-9
- Citations
- 10
- Primary Topic
- Multiple Sclerosis Research Studies
- Type
- article
- Field-Weighted Citation Impact
- 14.72
Funders
- Universität Wien
- Medizinische Universität Wien