T and B cell responses against Epstein-Barr virus in primary sclerosing cholangitis.
Authors
Hesham ElAbd, Mitchell Pesesky, Gabriel Innocenti, Brian K Chung, Aya K H Mahdy, Valeriia Kriukova, Laila Kulsvehagen, Dennis Strobbe, Claudia Stühler, Gabriele Mayr, Damon H May, Melanie Prinzensteiner, Tim A Steiert, Florian Tran, Michel V Hadjihannas, Rainer Günther, Elisa Rosati, Sören Mucha, Wolfgang Lieb, Malte Ziemann, Astrid Dempfle, Felix Braun, Trine Folseraas, Johannes R Hov, Espen Melum, Petra Bacher, Martina Sterneck, Tobias J Weismüller, Henrike Lenzen, Bernd Bokemeyer, Bryan Howie, Harlan S Robins, Christoph Röcken, Stefan Schreiber, Nina Khanna, Anne-Katrin Pröbstel, Christoph Schramm, Thomas Vogl, Tom H Karlsen, Andre Franke
Year of publication
2025Journal
NAT MEDVolume
-Issue
-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.