title: Significance of alanine aminopeptidase N (APN) in bile in the diagnosis of acute cellular rejection after liver transplantation.
abstract: BACKGROUND
  Allograft dysfunction after liver transplantation requires histopathologic examination for confirmation of the diagnosis, however, the procedure is invasive and its interpretation is not always accurate. The aim of this study was to find novel protein markers in bile for the diagnosis of acute cellular rejection (ACR) after liver transplantation.
  
  
  METHODS
  Quantitative proteomic analysis using the (18)O labeling method was used to search for bile proteins of interest. Nine recipients were selected who had liver dysfunction, diagnosed by liver biopsy, either with ACR (ACR group, n = 5) or without (LD group, n = 4). Donor bile samples were obtained from nine independent live liver donors. Enzyme activity in bile samples was assayed and liver biopsy specimens were immunostained for candidate protein of ACR.
  
  
  RESULTS
  The analysis identified 78 proteins, among which alanine aminopeptidase N (APN/CD13) was considered a candidate marker of ACR. Comparative analysis of the ACR and LD groups showed high APN enzyme activity in three (60%) of five cases of the ACR group, while it was as low as donor level in all patients of the LD group. APN enzyme activity in bile samples of liver dysfunction liver transplantation (LDLT) recipients of the ACR group collected within 3 d before biopsy-confirmed ACR (n = 10) was significantly higher (584 ± 434 U/g protein) than in those of recipients free of ACR (n = 96, 301 ± 271 U/g protein) (P = 0.004). APN overexpression along bile canaliculi was observed during ACR in all five cases of the ACR group.
  
  
  CONCLUSIONS
  APN in bile seems to be a useful and noninvasive biomarker of ACR after liver transplantation.
authors.affiliation: Department of Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Chiwan
authors.initials: C
authors.lastname: Kim
authors.forename: Shintaro
authors.initials: S
authors.lastname: Aono
authors.forename: Shigeru
authors.initials: S
authors.lastname: Marubashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Wada
authors.forename: Shogo
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Eguchi
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Takeda
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tanemura
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Okumura
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Takao
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Doki
authors.forename: Masaki
authors.initials: M
authors.lastname: Mori
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nagano
mesh_terms: D000208:Acute Disease; D000328:Adult; D001646:Bile / Q000737:chemistry*; D015415:Biomarkers / Q000032:analysis; D018826:CD13 Antigens / Q000032:analysis* / Q000378:metabolism; D005260:Female; D006084:Graft Rejection / Q000175:diagnosis / Q000378:metabolism*; D006801:Humans; D008099:Liver; D008107:Liver Diseases / Q000175:diagnosis / Q000378:metabolism*; D016031:Liver Transplantation / Q000009:adverse effects*; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D019737:Transplants / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D018826:CD13 Antigens