Dalekos Georgios N, Obermayer-Straub Petra, Bartels Moritz, Maeda Takashi, Kayser Anne, Braun Sabine, Loges Stephanie, Schmidt Eleonore, Gershwin M Eric, Manns Michael P
Department of Gastoenterology, Hepatology and Endocrinology, Medizinische Hochschule Hannover, Carl-Neuberg Str. 1, D-30623 Hannover, Germany.
J Hepatol. 2003 Nov;39(5):800-6. doi: 10.1016/s0168-8278(03)00356-8.
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.
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.
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.
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.
背景/目的：细胞色素P4502A6（CYP2A6）和P4501A2（CYP1A2）被描述为1型自身免疫性多腺体综合征（APS-1）中的肝脏自身抗原。我们评估了在无APS-1的几种肝脏疾病中抗CYP2A6和抗CYP1A2的意义。
采用基于[(35)S]-甲硫氨酸标记的CYP2A6和CYP1A2免疫沉淀的放射性配体测定法（RLA）。对430名慢性病毒性肝炎患者（n = 185）、自身免疫性肝病患者（n = 181）、自身免疫性风湿性疾病患者（ARD，n = 31）和健康人（n = 33）进行检测。
366例肝病患者中有7例抗CYP2A6阳性。健康人和ARD患者均未出现抗CYP2A6。181例自身免疫性肝病患者中有1例抗CYP2A6检测呈阳性。病毒性肝炎组7例患者中有6例抗CYP2A6阳性，其患病率显著更高（P < 0.05）。后者感染了黄病毒（1例庚型肝炎病毒/GB病毒C型，5例丙型肝炎病毒）。4/5例丙型肝炎病毒/抗CYP2A6阳性血清通过免疫荧光法检测抗LKM-1呈阳性，通过RLA法检测抗CYP2D6呈阳性。430份血清中无一例识别CYP1A2。
首次报道CYP2A6在黄病毒引起的病毒性肝炎患者中，特别是在丙型肝炎病毒/抗LKM-1阳性患者中作为肝脏自身抗原。需要进行多中心研究以调查这一新发现的临床重要性。本研究进一步支持在无黄病毒的情况下抗CYP2A6相当局限于APS-1。
