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001     280052
005     20250824001731.0
024 7 _ |a 10.1038/s41591-025-03692-w
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024 7 _ |a 1546-170X
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037 _ _ |a DZNE-2025-00889
041 _ _ |a English
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100 1 _ |a ElAbd, Hesham
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245 _ _ |a T and B cell responses against Epstein-Barr virus in primary sclerosing cholangitis.
260 _ _ |a [New York, NY]
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520 _ _ |a 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.
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650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Herpesvirus 4, Human: immunology
|2 MeSH
650 _ 2 |a Cholangitis, Sclerosing: immunology
|2 MeSH
650 _ 2 |a Cholangitis, Sclerosing: virology
|2 MeSH
650 _ 2 |a Cholangitis, Sclerosing: genetics
|2 MeSH
650 _ 2 |a B-Lymphocytes: immunology
|2 MeSH
650 _ 2 |a T-Lymphocytes: immunology
|2 MeSH
650 _ 2 |a Male
|2 MeSH
650 _ 2 |a Female
|2 MeSH
650 _ 2 |a Adult
|2 MeSH
650 _ 2 |a Epstein-Barr Virus Infections: immunology
|2 MeSH
650 _ 2 |a Middle Aged
|2 MeSH
650 _ 2 |a Case-Control Studies
|2 MeSH
650 _ 2 |a Infectious Mononucleosis: immunology
|2 MeSH
650 _ 2 |a Infectious Mononucleosis: complications
|2 MeSH
700 1 _ |a Pesesky, Mitchell
|0 0000-0003-2066-7905
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700 1 _ |a Innocenti, Gabriel
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700 1 _ |a Chung, Brian K
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700 1 _ |a Mahdy, Aya K H
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700 1 _ |a Kriukova, Valeriia
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700 1 _ |a Kulsvehagen, Laila
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700 1 _ |a Strobbe, Dennis
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700 1 _ |a Stühler, Claudia
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700 1 _ |a Mayr, Gabriele
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700 1 _ |a May, Damon H
|0 0000-0001-6902-3153
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700 1 _ |a Prinzensteiner, Melanie
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700 1 _ |a Steiert, Tim A
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700 1 _ |a Tran, Florian
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700 1 _ |a Hadjihannas, Michel V
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700 1 _ |a Günther, Rainer
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700 1 _ |a Rosati, Elisa
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700 1 _ |a Mucha, Sören
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700 1 _ |a Lieb, Wolfgang
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700 1 _ |a Ziemann, Malte
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700 1 _ |a Dempfle, Astrid
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700 1 _ |a Braun, Felix
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700 1 _ |a Folseraas, Trine
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700 1 _ |a Hov, Johannes R
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700 1 _ |a Melum, Espen
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700 1 _ |a Bacher, Petra
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700 1 _ |a Sterneck, Martina
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700 1 _ |a Weismüller, Tobias J
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700 1 _ |a Lenzen, Henrike
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700 1 _ |a Bokemeyer, Bernd
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700 1 _ |a Howie, Bryan
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700 1 _ |a Robins, Harlan S
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700 1 _ |a Röcken, Christoph
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700 1 _ |a Schreiber, Stefan
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700 1 _ |a Khanna, Nina
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700 1 _ |a Pröbstel, Anne-Katrin
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700 1 _ |a Schramm, Christoph
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700 1 _ |a Vogl, Thomas
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700 1 _ |a Karlsen, Tom H
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700 1 _ |a Franke, Andre
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773 _ _ |a 10.1038/s41591-025-03692-w
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