TY  - JOUR
AU  - ElAbd, Hesham
AU  - Pesesky, Mitchell
AU  - Innocenti, Gabriel
AU  - Chung, Brian K
AU  - Mahdy, Aya K H
AU  - Kriukova, Valeriia
AU  - Kulsvehagen, Laila
AU  - Strobbe, Dennis
AU  - Stühler, Claudia
AU  - Mayr, Gabriele
AU  - May, Damon H
AU  - Prinzensteiner, Melanie
AU  - Steiert, Tim A
AU  - Tran, Florian
AU  - Hadjihannas, Michel V
AU  - Günther, Rainer
AU  - Rosati, Elisa
AU  - Mucha, Sören
AU  - Lieb, Wolfgang
AU  - Ziemann, Malte
AU  - Dempfle, Astrid
AU  - Braun, Felix
AU  - Folseraas, Trine
AU  - Hov, Johannes R
AU  - Melum, Espen
AU  - Bacher, Petra
AU  - Sterneck, Martina
AU  - Weismüller, Tobias J
AU  - Lenzen, Henrike
AU  - Bokemeyer, Bernd
AU  - Howie, Bryan
AU  - Robins, Harlan S
AU  - Röcken, Christoph
AU  - Schreiber, Stefan
AU  - Khanna, Nina
AU  - Pröbstel, Anne-Katrin
AU  - Schramm, Christoph
AU  - Vogl, Thomas
AU  - Karlsen, Tom H
AU  - Franke, Andre
TI  - T and B cell responses against Epstein-Barr virus in primary sclerosing cholangitis.
JO  - Nature medicine
VL  - 31
IS  - 7
SN  - 1078-8956
CY  - [New York, NY]
PB  - Springer Nature
M1  - DZNE-2025-00889
SP  - 2306 - 2316
PY  - 2025
AB  - 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
KW  - Humans
KW  - Herpesvirus 4, Human: immunology
KW  - Cholangitis, Sclerosing: immunology
KW  - Cholangitis, Sclerosing: virology
KW  - Cholangitis, Sclerosing: genetics
KW  - B-Lymphocytes: immunology
KW  - T-Lymphocytes: immunology
KW  - Male
KW  - Female
KW  - Adult
KW  - Epstein-Barr Virus Infections: immunology
KW  - Middle Aged
KW  - Case-Control Studies
KW  - Infectious Mononucleosis: immunology
KW  - Infectious Mononucleosis: complications
LB  - PUB:(DE-HGF)16
C6  - pmid:40500415
C2  - pmc:PMC12283410
DO  - DOI:10.1038/s41591-025-03692-w
UR  - https://pub.dzne.de/record/280052
ER  -