%0 Journal Article
%A ElAbd, Hesham
%A Pesesky, Mitchell
%A Innocenti, Gabriel
%A Chung, Brian K
%A Mahdy, Aya K H
%A Kriukova, Valeriia
%A Kulsvehagen, Laila
%A Strobbe, Dennis
%A Stühler, Claudia
%A Mayr, Gabriele
%A May, Damon H
%A Prinzensteiner, Melanie
%A Steiert, Tim A
%A Tran, Florian
%A Hadjihannas, Michel V
%A Günther, Rainer
%A Rosati, Elisa
%A Mucha, Sören
%A Lieb, Wolfgang
%A Ziemann, Malte
%A Dempfle, Astrid
%A Braun, Felix
%A Folseraas, Trine
%A Hov, Johannes R
%A Melum, Espen
%A Bacher, Petra
%A Sterneck, Martina
%A Weismüller, Tobias J
%A Lenzen, Henrike
%A Bokemeyer, Bernd
%A Howie, Bryan
%A Robins, Harlan S
%A Röcken, Christoph
%A Schreiber, Stefan
%A Khanna, Nina
%A Pröbstel, Anne-Katrin
%A Schramm, Christoph
%A Vogl, Thomas
%A Karlsen, Tom H
%A Franke, Andre
%T T and B cell responses against Epstein-Barr virus in primary sclerosing cholangitis.
%J Nature medicine
%V 31
%N 7
%@ 1078-8956
%C [New York, NY]
%I Springer Nature
%M DZNE-2025-00889
%P 2306 - 2316
%D 2025
%X 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
%K Humans
%K Herpesvirus 4, Human: immunology
%K Cholangitis, Sclerosing: immunology
%K Cholangitis, Sclerosing: virology
%K Cholangitis, Sclerosing: genetics
%K B-Lymphocytes: immunology
%K T-Lymphocytes: immunology
%K Male
%K Female
%K Adult
%K Epstein-Barr Virus Infections: immunology
%K Middle Aged
%K Case-Control Studies
%K Infectious Mononucleosis: immunology
%K Infectious Mononucleosis: complications
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:40500415
%2 pmc:PMC12283410
%R 10.1038/s41591-025-03692-w
%U https://pub.dzne.de/record/280052