细胞色素P450 2D6（CYP2D6）上的构象表位可被肝/肾微粒体抗体识别。

Conformational epitopes on CYP2D6 are recognized by liver/kidney microsomal antibodies.

作者信息

Duclos-Vallée J C, Hajoui O, Yamamoto A M, Jacz-Aigrain E, Alvarez F

机构信息

INSERM Unité 347, Hôpital de Bicêtre, Paris, France.

出版信息

Gastroenterology. 1995 Feb;108(2):470-6. doi: 10.1016/0016-5085(95)90076-4.

DOI:10.1016/0016-5085(95)90076-4

PMID:7530671

Abstract

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

摘要

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。