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<p>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 &gt;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.</p>

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T and B cell responses against Epstein–Barr virus in primary sclerosing cholangitis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年6月11日

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  • 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

摘要

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.