T and B cell responses against Epstein–Barr virus in primary sclerosing cholangitis
[Line breaks added]
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.
Link | PDF (Nature Medicine) [Open Access]
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
[Line breaks added]
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.
Link | PDF (Nature Medicine) [Open Access]