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慢性丙型和丁型肝炎病毒感染中肝肾微粒体自身抗体的异质性

Heterogeneity of liver-kidney microsomal autoantibodies in chronic hepatitis C and D virus infection.

作者信息

Durazzo M, Philipp T, Van Pelt F N, Lüttig B, Borghesio E, Michel G, Schmidt E, Loges S, Rizzetto M, Manns M P

机构信息

Medizinische Hochschule Hannover, Abteilung Gastroenterologie und Hepatologie, Germany.

出版信息

Gastroenterology. 1995 Feb;108(2):455-62. doi: 10.1016/0016-5085(95)90074-8.

DOI:10.1016/0016-5085(95)90074-8
PMID:7835588
Abstract

BACKGROUND/AIMS: Anti-liver-kidney microsomal (LKM) autoantibodies occur in a proportion of patients with chronic hepatitis C and D infections. Because of different immunofluorescence patterns, antibodies in hepatitis C and D were termed LKM-1 and LKM-3, respectively. The aim of the present study was to evaluate the different specificities of LKM-1 and LKM-3 antibodies.

METHODS

Forty-nine samples of LKM-1 sera and 16 samples of LKM-3 sera were studied for reactivity against rat and human liver microsomal proteins by immunofluorescence, enzyme-linked immunosorbent assay, and Western blot.

RESULTS

Thirty-four percent of the LKM-1 sera reacted with 50-kilodalton cytochrome P4502D6 in Western blot. In addition, a proportion of the sera recognized either a 59- or 70-kilodalton antigen, and 45% of the sera did not react in Western blot. Recently, the major LKM-3 antigen was identified as an autoepitope expressed on uridine diphosphate-glucuronosyltransferases (UGT). Seven LKM-3-positive sera reacted with recombinant rabbit family one UGT. None of the anti-LKM-1-positive hepatitis C sera reacted with UGT. Antibody reactivity against liver microsomal proteins in enzyme-linked immunosorbent assay ended when antigens were pretreated with sodium dodecyl sulfate, confirming that antibodies recognize conformational epitopes.

CONCLUSIONS

LKM-1 antibodies in hepatitis C are more heterogeneous and react with different antigens compared with LKM-3 antibodies in hepatitis D.

摘要

背景/目的:抗肝肾微粒体(LKM)自身抗体在部分慢性丙型肝炎和丁型肝炎感染患者中出现。由于免疫荧光模式不同,丙型肝炎和丁型肝炎中的抗体分别被称为LKM-1和LKM-3。本研究的目的是评估LKM-1和LKM-3抗体的不同特异性。

方法

通过免疫荧光、酶联免疫吸附测定和蛋白质印迹法,研究了49份LKM-1血清样本和16份LKM-3血清样本对大鼠和人肝微粒体蛋白的反应性。

结果

在蛋白质印迹中,34%的LKM-1血清与50千道尔顿的细胞色素P4502D6发生反应。此外,一部分血清识别出59千道尔顿或70千道尔顿的抗原,45%的血清在蛋白质印迹中无反应。最近,主要的LKM-3抗原被鉴定为尿苷二磷酸葡萄糖醛酸转移酶(UGT)上表达的自身表位。7份LKM-3阳性血清与重组兔1家族UGT发生反应。抗LKM-1阳性的丙型肝炎血清均未与UGT发生反应。在酶联免疫吸附测定中,当抗原用十二烷基硫酸钠预处理后,抗体对肝微粒体蛋白的反应性消失,证实抗体识别构象表位。

结论

与丁型肝炎中的LKM-3抗体相比,丙型肝炎中的LKM-1抗体更具异质性,且能与不同抗原发生反应。

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