Cytochrome P450 2A6: A new hepatic autoantigen in patients with chronic hepatitis C virus infection

Georgios N. Dalekos, Petra Obermayer-Straub, Moritz Bartels, Takashi Maeda, Anne Kayser, Sabine Braun, Stephanie Loges, Eleonore Schmidt, M. Eric Gershwin, Michael P. Manns

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

Background/Aims: Cytochromes P4502A6 (CYP2A6) and P4501A2 (CYP1A2) were described as hepatic autoantigens in the autoimmune polyglandular syndrome type-1 (APS-1). We evaluated the significance of anti-CYP2A6 and anti-CYP1A2 in several hepatic diseases in the absence of APS-1. Methods: A radioligand assay (RLA) based on immunoprecipitation of [35S]-methionine-labeled CYP2A6 and CYP1A2 was used. Four hundred and thirty subjects with chronic viral hepatitis (n = 185), autoimmune liver diseases (n = 181), autoimmune rheumatic diseases (ARD, n = 31) and healthy (n = 33) were tested. Results: Seven out of 366 patients with liver diseases were anti-CYP2A6 positive. Neither healthy nor ARD patients showed anti-CYP2A6. One out of 181 patients with autoimmune liver diseases tested anti-CYP2A6 positive. A significantly higher prevalence of anti-CYP2A6 (P < 0.05) was detected with six out of seven patients positive in the viral hepatitis group. The latter were infected by flaviviruses (1 HGV/GBVC, 5 HCV). 4/5 HCV/anti-CYP2A6 positive sera were positive for anti-LKM-1 by immunofluorescence and for anti-CYP2D6 by RLA. None of the 430 sera recognized CYP1A2. Conclusions: For the first time CYP2A6 is reported as a hepatic autoantigen in patients with viral hepatitis caused by flaviviruses and in particular in HCV/anti-LKM-1 positive patients. Multicenter studies are needed in order to investigate the clinical importance of this novel finding. This study further supports that anti-C YP2A6 in the absence of flavivirus is rather limited to APS-1.

Original languageEnglish (US)
Pages (from-to)800-806
Number of pages7
JournalJournal of Hepatology
Volume39
Issue number5
DOIs
StatePublished - Nov 2003

Keywords

  • Autoimmune hepatitis
  • Autoimmunity
  • Chronic hepatitis
  • Cytochrome P450 1A2
  • Cytochrome P450 2A6
  • Cytochrome P450 2D6
  • Hepatitis C virus
  • LKM antibody

ASJC Scopus subject areas

  • Gastroenterology

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