Cytochrome P450 2A6: a new hepatic autoantigen in patients with chronic hepatitis C virus infection.
OBJECTIVE
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.
Dalekos
Georgios N
GN
Department of Gastoenterology, Hepatology and Endocrinology, Medizinische Hochschule Hannover, Carl-Neuberg Str. 1, D-30623 Hannover, Germany.
Obermayer-Straub
Petra
P
Bartels
Moritz
M
Maeda
Takashi
T
Kayser
Anne
A
Braun
Sabine
S
Loges
Stephanie
S
Schmidt
Eleonore
E
Gershwin
M Eric
ME
Manns
Michael P
MP
D000293:Adolescent; D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases / Q000276:immunology*; D001323:Autoantibodies / Q000032:analysis; D001324:Autoantigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology; D016022:Case-Control Studies; D002648:Child; D002908:Chronic Disease; D065637:Cytochrome P-450 CYP2A6; D005260:Female; D018178:Flaviviridae Infections / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000276:immunology*; D006525:Hepatitis, Viral, Human / Q000276:immunology; D006801:Humans; D008107:Liver Diseases / Q000276:immunology; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000276:immunology*; D012216:Rheumatic Diseases / Q000276:immunology
D001323:Autoantibodies; D001324:Autoantigens; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C585710:CYP2A6 protein, human; D065637:Cytochrome P-450 CYP2A6