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抗CagA抗体与血管壁抗原的交叉反应性:幽门螺杆菌感染与动脉粥样硬化之间可能的致病联系。

Cross-reactivity of anti-CagA antibodies with vascular wall antigens: possible pathogenic link between Helicobacter pylori infection and atherosclerosis.

作者信息

Franceschi Francesco, Sepulveda Antonia R, Gasbarrini Antonio, Pola Paolo, Silveri Nicolò Gentiloni, Gasbarrini Giovanni, Graham David Y, Genta Robert M

机构信息

Department of Pathology, VA Medical Center and Baylor College of Medicine, Houston, Tex 77030, USA.

出版信息

Circulation. 2002 Jul 23;106(4):430-4. doi: 10.1161/01.cir.0000024100.90140.19.

Abstract

BACKGROUND

Helicobacter pylori-CagA positive strains have been shown to be associated with atherosclerosis. However, the pathogenesis is still undetermined. The aim of this study was to determine whether anti-CagA antibodies cross-react with antigens of normal and atherosclerotic arteries.

METHODS AND RESULTS

Eight umbilical cord sections, 14 atherosclerotic artery sections, and 10 gastrointestinal tract sections were examined by immunohistochemistry using polyclonal anti-CagA antibodies. Five atherosclerotic and 3 normal artery samples were also lysed in ice-cold lysis buffer containing protease inhibitors and were immunoprecipitated using the same antibodies. Anti-CagA antibodies reacted with cytoplasm and nuclei of smooth muscle cells in umbilical cord and atherosclerotic vessel sections, cytoplasm of fibroblasts-like cells in intimal atherosclerotic plaques, and the cell membranes of endothelial cells. Anti-CagA antibodies also specifically immunoprecipitated 2 high molecular weight antigens of 160 and 180 kDa from both normal and atherosclerotic artery lysates.

CONCLUSIONS

Anti-CagA antibodies cross-react with antigens of both normal and atherosclerotic blood vessels. We speculate that the binding of anti-CagA antibodies to those antigens in injured arteries could influence the progression of atherosclerosis in CagA-positive H pylori-infected patients.

摘要

背景

幽门螺杆菌细胞毒素相关蛋白A(CagA)阳性菌株已被证明与动脉粥样硬化有关。然而,其发病机制仍未明确。本研究的目的是确定抗CagA抗体是否与正常动脉和动脉粥样硬化动脉的抗原发生交叉反应。

方法与结果

使用多克隆抗CagA抗体通过免疫组织化学检查8个脐带切片、14个动脉粥样硬化动脉切片和10个胃肠道切片。还将5个动脉粥样硬化和3个正常动脉样本在含有蛋白酶抑制剂的冰冷裂解缓冲液中裂解,并用相同抗体进行免疫沉淀。抗CagA抗体与脐带和平滑肌细胞的细胞质和细胞核、内膜动脉粥样硬化斑块中成纤维细胞样细胞的细胞质以及内皮细胞的细胞膜发生反应。抗CagA抗体还从正常和动脉粥样硬化动脉裂解物中特异性免疫沉淀出160和180 kDa的2种高分子量抗原。

结论

抗CagA抗体与正常和动脉粥样硬化血管的抗原发生交叉反应。我们推测,在CagA阳性幽门螺杆菌感染患者中,抗CagA抗体与受损动脉中这些抗原的结合可能会影响动脉粥样硬化的进展。

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