Duclos-Vallée J C, Hajoui O, Yamamoto A M, Jacz-Aigrain E, Alvarez F
INSERM Unité 347, Hôpital de Bicêtre, Paris, France.
Gastroenterology. 1995 Feb;108(2):470-6. doi: 10.1016/0016-5085(95)90076-4.
BACKGROUND/AIMS: Four linear antigenic sites have been shown on the CYP2D6 molecule that are recognized by serum positive for liver/kidney microsomal antibody (LKM) type 1. The aim of this study was to search for antibodies against CYP2D6 conformational antigenic sites in LKM-1-positive sera.
The capacity of four LKM-1-positive sera, before and after absorption with synthetic peptides representing CYP2D6 linear antigenic sites, and rabbit sera against linear antigenic sites between CYP2D6 amino acids 254-271 and 373-389 to inhibit the O-demethylation of dextromethorphan by CYP2D6 was tested in vitro.
Inhibition of O-demethylation of dextromethorphan was not modified by absorption of antibodies against linear CYP2D6 antigenic sites. In addition, rabbit sera against two of these sites did not inhibit the reaction. These results strongly suggest that antibodies against CYP2D6 conformational antigenic sites were present in LKM-1-positive sera.
The autoimmune response against CYP2D6 is directed against linear and conformational antigenic sites. These results strengthen the argument that the LKM-1 response is polyclonal and antigen driven.
背景/目的：细胞色素P450 2D6（CYP2D6）分子上已显示出四个线性抗原位点，可被1型肝肾微粒体抗体（LKM）血清阳性所识别。本研究的目的是在LKM-1阳性血清中寻找针对CYP2D6构象抗原位点的抗体。
在体外测试了四种LKM-1阳性血清在用代表CYP2D6线性抗原位点的合成肽吸收前后，以及针对CYP2D6氨基酸254 - 271和373 - 389之间线性抗原位点的兔血清抑制CYP2D6对右美沙芬O-去甲基化的能力。
针对CYP2D6线性抗原位点的抗体吸收后，右美沙芬O-去甲基化的抑制作用未改变。此外，针对其中两个位点的兔血清也未抑制该反应。这些结果强烈表明LKM-1阳性血清中存在针对CYP2D6构象抗原位点的抗体。
针对CYP2D6的自身免疫反应针对线性和构象抗原位点。这些结果支持了LKM-1反应是多克隆且由抗原驱动的观点。
