Journal Article

DZNE-2025-00889

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png T and B cell responses against Epstein-Barr virus in primary sclerosing cholangitis.

ElAbd, H. ; Pesesky, M. ; Innocenti, G. ; Chung, B. K. ; Mahdy, A. K. H. ; Kriukova, V. ; Kulsvehagen, L. ; Strobbe, D. ; Stühler, C. ; Mayr, G. ; May, D. H. ; Prinzensteiner, M. ; Steiert, T. A. ; Tran, F. ; Hadjihannas, M. V. ; Günther, R. ; Rosati, E. ; Mucha, S. ; Lieb, W. ; Ziemann, M. ; Dempfle, A. ; Braun, F. ; Folseraas, T. ; Hov, J. R. ; Melum, E. ; Bacher, P. ; Sterneck, M. ; Weismüller, T. J. ; Lenzen, H. ; Bokemeyer, B. ; Howie, B. ; Robins, H. S. ; Röcken, C. ; Schreiber, S. ; Khanna, N. ; Pröbstel, A.-K.DZNE* ; Schramm, C. ; Vogl, T. ; Karlsen, T. H. ; Franke, A.

2025
Springer Nature [New York, NY]

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Please use a persistent id in citations: doi:10.1038/s41591-025-03692-w

Abstract: 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.

Keyword(s): Humans (MeSH) ; Herpesvirus 4, Human: immunology (MeSH) ; Cholangitis, Sclerosing: immunology (MeSH) ; Cholangitis, Sclerosing: virology (MeSH) ; Cholangitis, Sclerosing: genetics (MeSH) ; B-Lymphocytes: immunology (MeSH) ; T-Lymphocytes: immunology (MeSH) ; Male (MeSH) ; Female (MeSH) ; Adult (MeSH) ; Epstein-Barr Virus Infections: immunology (MeSH) ; Middle Aged (MeSH) ; Case-Control Studies (MeSH) ; Infectious Mononucleosis: immunology (MeSH) ; Infectious Mononucleosis: complications (MeSH)

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Contributing Institute(s):

1. Clinical Neurology and Neuroimmunology (AG Pröbstel)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2025

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; DEAL Nature ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 80 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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