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

J Hepatol. 2003 Nov;39(5):800-6. doi: 10.1016/s0168-8278(03)00356-8.

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 [(35)S]-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-CYP2A6 in the absence of flavivirus is rather limited to APS-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aryl Hydrocarbon Hydroxylases / immunology*
  • Autoantibodies / analysis
  • Autoantigens / immunology*
  • Autoimmune Diseases / immunology
  • Case-Control Studies
  • Child
  • Chronic Disease
  • Cytochrome P-450 CYP2A6
  • Female
  • Flaviviridae Infections / immunology
  • Hepatitis C, Chronic / immunology*
  • Hepatitis, Viral, Human / immunology
  • Humans
  • Liver Diseases / immunology
  • Male
  • Middle Aged
  • Mixed Function Oxygenases / immunology*
  • Rheumatic Diseases / immunology

Substances

  • Autoantibodies
  • Autoantigens
  • Mixed Function Oxygenases
  • Aryl Hydrocarbon Hydroxylases
  • CYP2A6 protein, human
  • Cytochrome P-450 CYP2A6