Anti-programmed cell death-1 antibody as a new serological marker for type 1 autoimmune hepatitis

Kazuyuki Matsumoto, Yasuhiro Miyake, Hiroshi Matsushita, Atsuyuki Ohnishi, Fusao Ikeda, Hidenori Shiraha, Akinobu Takaki, Kazuhiro Nouso, Kazuhide Yamamoto

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Background and Aim: Recently, the association of the dysfunction of programmed cell death (PD)-1 expressed on activated lymphocytes with the pathogenesis of autoimmune hepatitis (AIH) has been speculated. This study aimed to investigate the association of serum anti-PD-1 antibodies with clinical characteristics of type 1 AIH. Methods: Serum samples before the initiation of prednisolone treatment were obtained from 52 type 1 AIH patients, 24 patients with drug-induced liver injury (DILI), 30 patients with acute viral hepatitis (AVH), 11 patients with primary sclerosing cholangitis (PSC), and 62 healthy volunteers. Titers of serum anti-PD-1 antibodies were measured by indirect enzyme-linked immunosorbent assay. The cutoff level was represented by a mean absorbance+2 standard deviations in healthy volunteers. Results: Prevalence of serum anti-PD-1 antibodies was 63% in type 1 AIH patients, 8% in DILI patients, 13% in AVH patients, 18% in PSC patients, and 3% in healthy volunteers. In type 1 AIH patients, titers of serum anti-PD-1 antibodies were correlated with serum levels of bilirubin (r=0.31, P=0.030) and alanine aminotransferase (r=0.31, P=0.027) but not serum immunoglobulin G levels. Positivity for serum anti-PD-1 antibodies was associated with the later normalization of serum alanine aminotransferase levels after the initiation of prednisolone and the disease relapse. Conclusions: Serum anti-PD-1 antibodies would be useful for the discrimination of type 1 AIH from DILI, AVH, and PSC as an auxiliary diagnostic marker. Furthermore, anti-PD-1 antibodies may be associated with clinical characteristics of type 1 AIH.

Original languageEnglish
Pages (from-to)110-115
Number of pages6
JournalJournal of Gastroenterology and Hepatology (Australia)
Volume29
Issue number1
DOIs
Publication statusPublished - Jan 2014

Fingerprint

Autoimmune Hepatitis
Cell Death
Antibodies
Serum
Chemical and Drug Induced Liver Injury
Sclerosing Cholangitis
Hepatitis
Healthy Volunteers
Prednisolone
Alanine Transaminase
Bilirubin
Immunoglobulin G
Enzyme-Linked Immunosorbent Assay
Lymphocytes
Recurrence

Keywords

  • Acute viral hepatitis
  • Autoimmune hepatitis
  • Drug-induced liver injury
  • Primary sclerosing cholangitis
  • Programmed cell death-1

ASJC Scopus subject areas

  • Gastroenterology
  • Hepatology

Cite this

Anti-programmed cell death-1 antibody as a new serological marker for type 1 autoimmune hepatitis. / Matsumoto, Kazuyuki; Miyake, Yasuhiro; Matsushita, Hiroshi; Ohnishi, Atsuyuki; Ikeda, Fusao; Shiraha, Hidenori; Takaki, Akinobu; Nouso, Kazuhiro; Yamamoto, Kazuhide.

In: Journal of Gastroenterology and Hepatology (Australia), Vol. 29, No. 1, 01.2014, p. 110-115.

Research output: Contribution to journalArticle

@article{86bf663b56604cbf8497647a8b533db9,
title = "Anti-programmed cell death-1 antibody as a new serological marker for type 1 autoimmune hepatitis",
abstract = "Background and Aim: Recently, the association of the dysfunction of programmed cell death (PD)-1 expressed on activated lymphocytes with the pathogenesis of autoimmune hepatitis (AIH) has been speculated. This study aimed to investigate the association of serum anti-PD-1 antibodies with clinical characteristics of type 1 AIH. Methods: Serum samples before the initiation of prednisolone treatment were obtained from 52 type 1 AIH patients, 24 patients with drug-induced liver injury (DILI), 30 patients with acute viral hepatitis (AVH), 11 patients with primary sclerosing cholangitis (PSC), and 62 healthy volunteers. Titers of serum anti-PD-1 antibodies were measured by indirect enzyme-linked immunosorbent assay. The cutoff level was represented by a mean absorbance+2 standard deviations in healthy volunteers. Results: Prevalence of serum anti-PD-1 antibodies was 63{\%} in type 1 AIH patients, 8{\%} in DILI patients, 13{\%} in AVH patients, 18{\%} in PSC patients, and 3{\%} in healthy volunteers. In type 1 AIH patients, titers of serum anti-PD-1 antibodies were correlated with serum levels of bilirubin (r=0.31, P=0.030) and alanine aminotransferase (r=0.31, P=0.027) but not serum immunoglobulin G levels. Positivity for serum anti-PD-1 antibodies was associated with the later normalization of serum alanine aminotransferase levels after the initiation of prednisolone and the disease relapse. Conclusions: Serum anti-PD-1 antibodies would be useful for the discrimination of type 1 AIH from DILI, AVH, and PSC as an auxiliary diagnostic marker. Furthermore, anti-PD-1 antibodies may be associated with clinical characteristics of type 1 AIH.",
keywords = "Acute viral hepatitis, Autoimmune hepatitis, Drug-induced liver injury, Primary sclerosing cholangitis, Programmed cell death-1",
author = "Kazuyuki Matsumoto and Yasuhiro Miyake and Hiroshi Matsushita and Atsuyuki Ohnishi and Fusao Ikeda and Hidenori Shiraha and Akinobu Takaki and Kazuhiro Nouso and Kazuhide Yamamoto",
year = "2014",
month = "1",
doi = "10.1111/jgh.12340",
language = "English",
volume = "29",
pages = "110--115",
journal = "Journal of Gastroenterology and Hepatology (Australia)",
issn = "0815-9319",
publisher = "Wiley-Blackwell",
number = "1",

}

TY - JOUR

T1 - Anti-programmed cell death-1 antibody as a new serological marker for type 1 autoimmune hepatitis

AU - Matsumoto, Kazuyuki

AU - Miyake, Yasuhiro

AU - Matsushita, Hiroshi

AU - Ohnishi, Atsuyuki

AU - Ikeda, Fusao

AU - Shiraha, Hidenori

AU - Takaki, Akinobu

AU - Nouso, Kazuhiro

AU - Yamamoto, Kazuhide

PY - 2014/1

Y1 - 2014/1

N2 - Background and Aim: Recently, the association of the dysfunction of programmed cell death (PD)-1 expressed on activated lymphocytes with the pathogenesis of autoimmune hepatitis (AIH) has been speculated. This study aimed to investigate the association of serum anti-PD-1 antibodies with clinical characteristics of type 1 AIH. Methods: Serum samples before the initiation of prednisolone treatment were obtained from 52 type 1 AIH patients, 24 patients with drug-induced liver injury (DILI), 30 patients with acute viral hepatitis (AVH), 11 patients with primary sclerosing cholangitis (PSC), and 62 healthy volunteers. Titers of serum anti-PD-1 antibodies were measured by indirect enzyme-linked immunosorbent assay. The cutoff level was represented by a mean absorbance+2 standard deviations in healthy volunteers. Results: Prevalence of serum anti-PD-1 antibodies was 63% in type 1 AIH patients, 8% in DILI patients, 13% in AVH patients, 18% in PSC patients, and 3% in healthy volunteers. In type 1 AIH patients, titers of serum anti-PD-1 antibodies were correlated with serum levels of bilirubin (r=0.31, P=0.030) and alanine aminotransferase (r=0.31, P=0.027) but not serum immunoglobulin G levels. Positivity for serum anti-PD-1 antibodies was associated with the later normalization of serum alanine aminotransferase levels after the initiation of prednisolone and the disease relapse. Conclusions: Serum anti-PD-1 antibodies would be useful for the discrimination of type 1 AIH from DILI, AVH, and PSC as an auxiliary diagnostic marker. Furthermore, anti-PD-1 antibodies may be associated with clinical characteristics of type 1 AIH.

AB - Background and Aim: Recently, the association of the dysfunction of programmed cell death (PD)-1 expressed on activated lymphocytes with the pathogenesis of autoimmune hepatitis (AIH) has been speculated. This study aimed to investigate the association of serum anti-PD-1 antibodies with clinical characteristics of type 1 AIH. Methods: Serum samples before the initiation of prednisolone treatment were obtained from 52 type 1 AIH patients, 24 patients with drug-induced liver injury (DILI), 30 patients with acute viral hepatitis (AVH), 11 patients with primary sclerosing cholangitis (PSC), and 62 healthy volunteers. Titers of serum anti-PD-1 antibodies were measured by indirect enzyme-linked immunosorbent assay. The cutoff level was represented by a mean absorbance+2 standard deviations in healthy volunteers. Results: Prevalence of serum anti-PD-1 antibodies was 63% in type 1 AIH patients, 8% in DILI patients, 13% in AVH patients, 18% in PSC patients, and 3% in healthy volunteers. In type 1 AIH patients, titers of serum anti-PD-1 antibodies were correlated with serum levels of bilirubin (r=0.31, P=0.030) and alanine aminotransferase (r=0.31, P=0.027) but not serum immunoglobulin G levels. Positivity for serum anti-PD-1 antibodies was associated with the later normalization of serum alanine aminotransferase levels after the initiation of prednisolone and the disease relapse. Conclusions: Serum anti-PD-1 antibodies would be useful for the discrimination of type 1 AIH from DILI, AVH, and PSC as an auxiliary diagnostic marker. Furthermore, anti-PD-1 antibodies may be associated with clinical characteristics of type 1 AIH.

KW - Acute viral hepatitis

KW - Autoimmune hepatitis

KW - Drug-induced liver injury

KW - Primary sclerosing cholangitis

KW - Programmed cell death-1

UR - http://www.scopus.com/inward/record.url?scp=84897584800&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84897584800&partnerID=8YFLogxK

U2 - 10.1111/jgh.12340

DO - 10.1111/jgh.12340

M3 - Article

VL - 29

SP - 110

EP - 115

JO - Journal of Gastroenterology and Hepatology (Australia)

JF - Journal of Gastroenterology and Hepatology (Australia)

SN - 0815-9319

IS - 1

ER -