Mimicry between the hepatitis C virus polyprotein and antigenic targets of nuclear and smooth muscle antibodies in chronic hepatitis C virus infection
Mimicry between the hepatitis C virus polyprotein and antigenic targets of nuclear and smooth muscle antibodies in chronic hepatitis C virus infection
复制标题
DOI：
10.1046/j.1365-2249.2003.02229.x
复制
发表时间：
2003-09-01
影响因子：
4.6
通讯作者：
Vergani, D
中科院分区：
文献类型：
--
作者：
Gregorio, GV;Choudhuri, K;Vergani, D
抗平滑肌（SMA）和抗核成分（ANA）的自身抗体在慢性丙型肝炎病毒感染的自然过程中产生。鉴于越来越多的证据表明“分子模拟”作为自身免疫的一种机制，我们研究了宿主平滑肌/核成分与HCV抗原之间的交叉反应性免疫反应是否可能有助于慢性HCV感染中SMA和ANA的形成。计算机辅助蛋白质数据库检索方法被用来确定三个平滑肌（smoothelin（698-717），肌球蛋白（1035-1054）波形蛋白（69-88））和三个核（matrin（722-741），组蛋白H2 A（11-30），复制蛋白A（133-152））与HCV多聚蛋白具有最高局部序列相似性的宿主抗原和20-构建对应于这些区域的mer肽。从51名儿童慢性HCV感染[中位年龄：8（2-16）; 27名男孩]，26 SMA阳性和5 ANA阳性，血清进行了测试的反应性合成的HCV肽和他们的人类同源物的酶联免疫吸附试验（ELISA）。以HBV感染和不同病因慢性肝病患者血清作为对照。对HCV肽和平滑肌/核同源物的“双重反应性”与HCV感染密切相关（两者P < 0.001）。建立了体液交叉反应性作为竞争ELISA双重识别的基础。平滑肌和HCV肽抗原的双反应性与间接免疫荧光法检测的SMA阳性相关（P=0.05）。在15名对肌球蛋白（1035-1054）及其HCV同源物呈双重反应的患者中，13名通过免疫印迹识别出完整的肌球蛋白。这些结果表明，ANA和SMA在慢性HCV感染可能会出现，至少部分，作为一个结果的交叉反应性免疫应答HCV和宿主平滑肌/核抗原。
Autoantibodies to smooth muscle (SMA) and nuclear components (ANA) arise in the natural course of chronic infection with hepatitis C virus. In view of the growing evidence for 'molecular mimicry' as a mechanism of autoimmunity we investigated whether cross-reactive immune reactions between host smooth muscle/nuclear components and HCV antigens may contribute to the formation of SMA and ANA in chronic HCV infection. Computer-assisted protein database search methods were used to identify three smooth muscle (smoothelin(698-717), myosin(1035-1054) vimentin(69-88)) and three nuclear (matrin(722-741), histone H2A(11-30), replication protein A(133-152)) host antigens with the highest local sequence similarity to the HCV polyprotein and 20-mer peptides corresponding to these regions were constructed. Sera from 51 children with chronic HCV infection [median age: 8 (2-16); 27 boys], 26 SMA positive and five ANA positive, were tested for reactivity to the synthesized HCV peptides and their human homologues by enzyme linked immunosorbent assay (ELISA). Sera from patients with HBV infection and chronic liver disease of different aetiologies were used as controls. 'Double reactivity' to HCV peptides and smooth muscle/nuclear homologues was associated strongly with HCV infection (P < 0.001 for both). Humoral cross-reactivity was established as the basis for double recognition by competition ELISA. Double-reactivity to smooth muscle and HCV peptide antigens correlated with SMA positivity by indirect immunofluouresence (P=0.05). Of 15 patients double-reactive to myosin(1035-1054) and its HCV homologue, 13 recognized whole myosin by immunoblot. These results suggest that ANA and SMA in chronic HCV infection may arise, at least in part, as a consequence of cross-reactive immune responses to HCV and host smooth muscle/nuclear antigens.