Significance of alanine aminopeptidase N (APN) in bile in the diagnosis of acute cellular rejection after liver transplantation

Chiwan Kim, Shintaro Aono, Shigeru Marubashi, Hiroshi Wada, Shogo Kobayashi, Hidetoshi Eguchi, Yutaka Takeda, Masahiro Tanemura, Nobuaki Okumura, Toshifumi Takao, Yuichiro Doki, Masaki Mori, Hiroaki Nagano

Research output: Contribution to journalArticle

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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. Materials and Methods: Quantitative proteomic analysis using the 18O 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. Conclusion: APN in bile seems to be a useful and noninvasive biomarker of ACR after liver transplantation.

Original languageEnglish
Pages (from-to)138-148
Number of pages11
JournalJournal of Surgical Research
Volume175
Issue number1
DOIs
Publication statusPublished - Jun 1 2012
Externally publishedYes

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CD13 Antigens
Bile
Liver Transplantation
Proteins
Tissue Donors
Biopsy
Liver Diseases
Liver
Enzymes
Bile Canaliculi
Proteomics
Allografts
Biomarkers

All Science Journal Classification (ASJC) codes

  • Surgery

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Significance of alanine aminopeptidase N (APN) in bile in the diagnosis of acute cellular rejection after liver transplantation. / Kim, Chiwan; Aono, Shintaro; Marubashi, Shigeru; Wada, Hiroshi; Kobayashi, Shogo; Eguchi, Hidetoshi; Takeda, Yutaka; Tanemura, Masahiro; Okumura, Nobuaki; Takao, Toshifumi; Doki, Yuichiro; Mori, Masaki; Nagano, Hiroaki.

In: Journal of Surgical Research, Vol. 175, No. 1, 01.06.2012, p. 138-148.

Research output: Contribution to journalArticle

Kim, C, Aono, S, Marubashi, S, Wada, H, Kobayashi, S, Eguchi, H, Takeda, Y, Tanemura, M, Okumura, N, Takao, T, Doki, Y, Mori, M & Nagano, H 2012, 'Significance of alanine aminopeptidase N (APN) in bile in the diagnosis of acute cellular rejection after liver transplantation', Journal of Surgical Research, vol. 175, no. 1, pp. 138-148. https://doi.org/10.1016/j.jss.2011.02.044
Kim, Chiwan ; Aono, Shintaro ; Marubashi, Shigeru ; Wada, Hiroshi ; Kobayashi, Shogo ; Eguchi, Hidetoshi ; Takeda, Yutaka ; Tanemura, Masahiro ; Okumura, Nobuaki ; Takao, Toshifumi ; Doki, Yuichiro ; Mori, Masaki ; Nagano, Hiroaki. / Significance of alanine aminopeptidase N (APN) in bile in the diagnosis of acute cellular rejection after liver transplantation. In: Journal of Surgical Research. 2012 ; Vol. 175, No. 1. pp. 138-148.
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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. Materials and Methods: Quantitative proteomic analysis using the 18O 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. Conclusion: APN in bile seems to be a useful and noninvasive biomarker of ACR after liver transplantation.",
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T1 - Significance of alanine aminopeptidase N (APN) in bile in the diagnosis of acute cellular rejection after liver transplantation

AU - Kim, Chiwan

AU - Aono, Shintaro

AU - Marubashi, Shigeru

AU - Wada, Hiroshi

AU - Kobayashi, Shogo

AU - Eguchi, Hidetoshi

AU - Takeda, Yutaka

AU - Tanemura, Masahiro

AU - Okumura, Nobuaki

AU - Takao, Toshifumi

AU - Doki, Yuichiro

AU - Mori, Masaki

AU - Nagano, Hiroaki

PY - 2012/6/1

Y1 - 2012/6/1

N2 - 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. Materials and Methods: Quantitative proteomic analysis using the 18O 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. Conclusion: APN in bile seems to be a useful and noninvasive biomarker of ACR after liver transplantation.

AB - 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. Materials and Methods: Quantitative proteomic analysis using the 18O 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. Conclusion: APN in bile seems to be a useful and noninvasive biomarker of ACR after liver transplantation.

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