T and B cell responses against Epstein–Barr virus in primary sclerosing cholangitis
Primary sclerosing cholangitis (PSC) is an idiopathic, progressive and incurable liver disease. Here, we aimed for systematic analyses of adaptive immune responses in PSC. By profiling the T cell repertoires of 504 individuals with PSC and 904 healthy controls, we identified 1,008 clonotypes associated with PSC. A substantial fraction of these clonotypes was restricted to known PSC human leukocyte antigen susceptibility alleles and known to target Epstein-Barr virus (EBV) epitopes. We further utilized phage-immunoprecipitation sequencing to determine antibody epitope repertoires of 120 individuals with PSC and 202 healthy controls, which showed a higher burden of anti-EBV responses in PSC than controls. EBV-specific monoclonal antibodies isolated from B cells in PSC livers corroborated convergent B and T cell responses against EBV. By analyzing electronic health records of >116 million people, we identified an association between infectious mononucleosis and PSC (odds ratio, 12; 95% confidence interval, 6.3-22.9), suggesting a link between EBV and PSC.
Authors
- Thomas J. Vogl (ORCID: https://orcid.org/0000-0002-3892-1740)
- Felix Braun (ORCID: https://orcid.org/0000-0002-5296-2020)
- Laila Kulsvehagen (ORCID: https://orcid.org/0000-0001-5236-8323)
- Harlan Robins (ORCID: https://orcid.org/0000-0001-5225-7076)
- Tobias J. Weismüller (ORCID: https://orcid.org/0000-0001-9736-1483)
- Damon May (ORCID: https://orcid.org/0000-0001-6902-3153)
- Petra Bächer (ORCID: https://orcid.org/0000-0003-4264-6451)
- Christoph Röcken (ORCID: https://orcid.org/0000-0002-6989-8002)
- Christoph Schramm (ORCID: https://orcid.org/0000-0002-4264-1928)
- Aya K.H. Mahdy (ORCID: https://orcid.org/0009-0009-6115-4429)
- Giuseppe Pietro Innocenti (ORCID: https://orcid.org/0000-0002-9975-9871)
- Malte Ziemann (ORCID: https://orcid.org/0000-0003-0919-0237)
- Tim Alexander Steiert (ORCID: https://orcid.org/0000-0002-0125-1173)
- Tom H. Karlsen (ORCID: https://orcid.org/0000-0002-8289-9931)
- Melanie Prinzensteiner (ORCID: https://orcid.org/0009-0002-8208-1141)
- Trine Folseraas (ORCID: https://orcid.org/0000-0003-2011-1923)
- Espen Melum (ORCID: https://orcid.org/0000-0001-6903-6878)
- Florian Tran (ORCID: https://orcid.org/0000-0002-3735-9872)
- Sören Mucha (ORCID: https://orcid.org/0000-0002-1647-2526)
- Bernd Bokemeyer (ORCID: https://orcid.org/0000-0003-2016-6991)
- Stefan Schreiber (ORCID: https://orcid.org/0000-0003-2254-7771)
- Nina Khanna (ORCID: https://orcid.org/0000-0002-2642-419X)
- Michel V. Hadjihannas (ORCID: https://orcid.org/0000-0001-6200-2675)
- Gabriele Mayr (ORCID: https://orcid.org/0000-0003-2468-5350)
- André Franke (ORCID: https://orcid.org/0000-0003-1530-5811)
- Henrike Lenzen (ORCID: https://orcid.org/0000-0002-0903-1415)
- Elisa Rosati (ORCID: https://orcid.org/0000-0002-2635-6422)
- Mitchell W. Pesesky (ORCID: https://orcid.org/0000-0003-2066-7905)
- Astrid Dempfle (ORCID: https://orcid.org/0000-0002-2618-3920)
- Hesham ElAbd (ORCID: https://orcid.org/0000-0003-1844-8279)
- Brian K. Chung (ORCID: https://orcid.org/0000-0002-9523-7515)
- Martina Sterneck
- Anne‐Katrin Pröbstel (ORCID: https://orcid.org/0000-0002-7748-1872)
- Johannes R. Hov (ORCID: https://orcid.org/0000-0002-5900-8096)
- Valeriia Kriukova (ORCID: https://orcid.org/0000-0002-5168-6511)
- Rainer Günther
- Wolfgang Lieb
- Bryan Howie
- Claudia Stühler
- Dennis Strobbe
Institutions
- Oslo University Hospital (NO)
- Universität Hamburg (DE)
- University of Oslo (NO)
- University of Basel (CH)
- University Hospital Bonn (DE)
- German Center for Neurodegenerative Diseases (DE)
- University Hospital of Basel (CH)
- Hochschule für Angewandte Wissenschaften Kiel (DE)
- Christian-Albrechts-Universität zu Kiel (DE)
- Medizinische Hochschule Hannover (DE)
- Comprehensive Cancer Center Vienna (AT)
- Adaptive Biotechnologies (United States) (US)
- University Medical Center Hamburg-Eppendorf (DE)
- Vivantes Klinikum (DE)
- University Hospital Schleswig-Holstein (DE)
- Johannes Wesling Klinikum Minden (DE)
- Clinical Research Center Kiel (DE)
- Medical University of Vienna (AT)
- University of Lübeck (DE)
Publication Details
- Journal
- Nature Medicine
- Published
- 2025-06-11
- DOI
- https://doi.org/10.1038/s41591-025-03692-w
- Citations
- 18
- Primary Topic
- Liver Diseases and Immunity
- Type
- article
- Field-Weighted Citation Impact
- 23.80