title: In situ characterization of intrahepatic non-parenchymal cells in PSC reveals phenotypic patterns associated with disease severity.
abstract: Liver-infiltrating T cells have been implicated in the pathogenesis of primary sclerosing cholangitis (PSC), however little information is available about changes in other cellular compartments in the liver during PSC. This study aimed to characterize non-parenchymal intrahepatic cells in PSC livers and to find associations between phenotypes and disease severity. Using immunohistochemistry, followed by automated image analysis and quantification and a principal component analysis, we have studied non-parenchymal intrahepatic cells in PSC-patient livers (n = 17) and controls (n = 17). We observed a significant increase of T cells in the PSC patients, localized to the fibrotic areas. MAIT cells, normally present at high numbers in the liver, were not increased to the same extent. PSC patients had lower expression of MHC class I than controls. However, the levels of NKp46+ NK cells were similar between patients and controls, nevertheless, NKp46 was identified as a phenotypic marker that distinguished PSC patients with mild from those with severe fibrosis. Beyond that, a group of PSC patients had lost expression of Caldesmon and this was associated with more extensive bile duct proliferation and higher numbers of T cells. Our data reveals phenotypic patterns in PSC patients associated with disease severity.
authors.affiliation: Liver Immunology Laboratory, Unit of Gastroenterology and Hepatology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Lena
authors.initials: L
authors.lastname: Berglin
authors.affiliation: Liver Immunology Laboratory, Unit of Gastroenterology and Hepatology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Annika
authors.initials: A
authors.lastname: Bergquist
authors.affiliation: Division of Transplantation Surgery, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Helene
authors.initials: H
authors.lastname: Johansson
authors.affiliation: Department of Medicine, Clinical Pathology and Cytology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Hans
authors.initials: H
authors.lastname: Glaumann
authors.affiliation: Division of Transplantation Surgery, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Carl
authors.initials: C
authors.lastname: Jorns
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Lunemann
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Heiner
authors.initials: H
authors.lastname: Wedemeyer
authors.affiliation: Division of Transplantation Surgery, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Ewa C
authors.initials: EC
authors.lastname: Ellis
authors.affiliation: Liver Immunology Laboratory, Unit of Gastroenterology and Hepatology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden; Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Niklas K
authors.initials: NK
authors.lastname: Björkström
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001652:Bile Ducts / Q000473:pathology; D002148:Calmodulin-Binding Proteins / Q000378:metabolism; D016022:Case-Control Studies; D015209:Cholangitis, Sclerosing / Q000276:immunology / Q000473:pathology*; D005260:Female; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000276:immunology / Q000473:pathology*; D008103:Liver Cirrhosis / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000276:immunology; D055815:Young Adult
chemical_list: D002148:Calmodulin-Binding Proteins