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 journalArticle

34 Citations (Scopus)

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

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Autoantigens
Chronic Hepatitis C
Virus Diseases
Cytochromes
Hepacivirus
Cytochrome P-450 Enzyme System
Liver
Autoimmune Polyendocrinopathies
Flavivirus
Autoimmune Diseases
Liver Diseases
Radioligand Assay
Hepatitis
Cytochrome P-450 CYP2D6
Chronic Hepatitis
Rheumatic Diseases
Serum
Immunoprecipitation
Methionine
Multicenter Studies

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

Cite this

Dalekos, G. N., Obermayer-Straub, P., Bartels, M., Maeda, T., Kayser, A., Braun, S., ... Manns, M. P. (2003). Cytochrome P450 2A6: A new hepatic autoantigen in patients with chronic hepatitis C virus infection. Journal of Hepatology, 39(5), 800-806. https://doi.org/10.1016/S0168-8278(03)00356-8

Cytochrome P450 2A6 : A new hepatic autoantigen in patients with chronic hepatitis C virus infection. / Dalekos, Georgios N.; Obermayer-Straub, Petra; Bartels, Moritz; Maeda, Takashi; Kayser, Anne; Braun, Sabine; Loges, Stephanie; Schmidt, Eleonore; Gershwin, M. Eric; Manns, Michael P.

In: Journal of Hepatology, Vol. 39, No. 5, 11.2003, p. 800-806.

Research output: Contribution to journalArticle

Dalekos, GN, Obermayer-Straub, P, Bartels, M, Maeda, T, Kayser, A, Braun, S, Loges, S, Schmidt, E, Gershwin, ME & Manns, MP 2003, 'Cytochrome P450 2A6: A new hepatic autoantigen in patients with chronic hepatitis C virus infection', Journal of Hepatology, vol. 39, no. 5, pp. 800-806. https://doi.org/10.1016/S0168-8278(03)00356-8
Dalekos, Georgios N. ; Obermayer-Straub, Petra ; Bartels, Moritz ; Maeda, Takashi ; Kayser, Anne ; Braun, Sabine ; Loges, Stephanie ; Schmidt, Eleonore ; Gershwin, M. Eric ; Manns, Michael P. / Cytochrome P450 2A6 : A new hepatic autoantigen in patients with chronic hepatitis C virus infection. In: Journal of Hepatology. 2003 ; Vol. 39, No. 5. pp. 800-806.
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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.",
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T2 - A new hepatic autoantigen in patients with chronic hepatitis C virus infection

AU - Dalekos, Georgios N.

AU - Obermayer-Straub, Petra

AU - Bartels, Moritz

AU - Maeda, Takashi

AU - Kayser, Anne

AU - Braun, Sabine

AU - Loges, Stephanie

AU - Schmidt, Eleonore

AU - Gershwin, M. Eric

AU - Manns, Michael P.

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N2 - 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.

AB - 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.

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KW - Chronic hepatitis

KW - Cytochrome P450 1A2

KW - Cytochrome P450 2A6

KW - Cytochrome P450 2D6

KW - Hepatitis C virus

KW - LKM antibody

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