title: Prominent HLA-G Expression in Liver Disease But Not After Liver Transplantation.
abstract: BACKGROUND
  HLA-G is a nonclassical MHC class I molecule and its physiological expression restricted to placental extravillous trophoblasts contributes to maternal tolerance to the semiallogeneic fetus. Aberrant expression of HLA-G in human organ grafts has been proposed to contribute to graft acceptance.
  
  
  METHODS
  We studied HLA-G expression in liver tissue and serum of adult liver transplant recipients before, early, and late after transplantation in relation to liver function and operational tolerance.
  
  
  RESULTS
  Cirrhotic explant livers showed robust HLA-G expression on hepatocytes, whereas the majority of noncirrhotic livers and graft biopsies taken before or after liver transplantation (LTX) showed no, or weak, HLA-G expression. The HLA-G expression was induced on hepatocytes in vitro by TGF-β, but not by other relevant cytokines. Serum levels of the HLA-G isoforms 1 + 5 gradually declined after LTX. Early after LTX, serum HLA-G levels were higher in patients with acute rejection episodes than nonrejectors. Late after LTX, serum HLA-G levels did not differ between operationally tolerant patients and patients on regular immunosuppressive therapy.
  
  
  CONCLUSIONS
  Our data do not support a graft-protective role for HLA-G after LTX, but show that end-stage liver diseases are associated with HLA-G expression on hepatocytes, which may determine a negative feedback to protect the liver against immunological damage.
authors.affiliation: 1 Department of Gastroenterology and Hepatology, Erasmus MC University Medical Centre, Rotterdam, the Netherlands. 2 Laboratory of Medical Immunology, Department of Laboratory Medicine, Radboud University Medical Centre, Nijmegen, the Netherlands. 3 Department of Pathology, Erasmus MC University Medical Centre, Rotterdam, the Netherlands. 4 Department of Viroscience, Erasmus MC University Medical Centre, Rotterdam, the Netherlands. 5 Department of Surgery, Erasmus MC University Medical Centre, Rotterdam, the Netherlands.
authors.forename: Viviana
authors.initials: V
authors.lastname: Moroso
authors.forename: Bram
authors.initials: B
authors.lastname: van Cranenbroek
authors.forename: Shanta
authors.initials: S
authors.lastname: Mancham
authors.forename: Kostandinos
authors.initials: K
authors.lastname: Sideras
authors.forename: Patrick P C
authors.initials: PP
authors.lastname: Boor
authors.forename: Katharina
authors.initials: K
authors.lastname: Biermann
authors.forename: Lisette
authors.initials: L
authors.lastname: de Vogel
authors.forename: Robert J
authors.initials: RJ
authors.lastname: de Knegt
authors.forename: Annemiek
authors.initials: A
authors.lastname: van der Eijk
authors.forename: Luc J W
authors.initials: LJ
authors.lastname: van der Laan
authors.forename: Jeroen
authors.initials: J
authors.lastname: de Jonge
authors.forename: Herold J
authors.initials: HJ
authors.lastname: Metselaar
authors.forename: Irma
authors.initials: I
authors.lastname: Joosten
authors.forename: Jaap
authors.initials: J
authors.lastname: Kwekkeboom
mesh_terms: D000328:Adult; D001706:Biopsy; D058625:End Stage Liver Disease / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000276:immunology* / Q000378:metabolism; D006085:Graft Survival; D059951:HLA-G Antigens / Q000096:biosynthesis* / Q000276:immunology; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D007150:Immunohistochemistry; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D059951:HLA-G Antigens