Antibodies anti-CagA cross-react with trophoblast cells: a risk factor for pre-eclampsia?
Antibodies anti-CagA cross-react with trophoblast cells: a risk factor for pre-eclampsia?
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抗 CagA 抗体与滋养层细胞发生交叉反应：先兆子痫的危险因素？
DOI：
10.1111/j.1523-5378.2012.00966.x
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发表时间：
2012-12
期刊：
影响因子：
4.4
通讯作者：
Gasbarrini A
中科院分区：
文献类型：
--
作者：
Franceschi F;Di Simone N;D'Ippolito S;Castellani R;Di Nicuolo F;Gasbarrini G;Yamaoka Y;Todros T;Scambia G;Gasbarrini A
先前的研究报道了CagA阳性幽门螺杆菌菌株与子痫前期之间的流行病学关联。由于抗CagA抗体与内皮细胞发生交叉反应，且滋养层细胞呈现出内皮细胞表型特征，我们假设抗CagA抗体可能识别细胞滋养层细胞的抗原，进而损害其功能。
胎盘样本取自健康女性。将细胞滋养层细胞培养在含有浓度递增的多克隆抗CagA抗体的培养基中。通过细胞酶联免疫吸附试验（ELISA）和免疫荧光测定法评估抗CagA抗体与细胞滋养层细胞的结合情况。利用侵袭培养系统并通过检测基质金属蛋白酶 - 2（MMP - 2）来评估这些细胞的侵袭能力。对被抗CagA抗体沉淀的抗原进行蛋白质测序。同时，还对用抗CagA抗体或无关抗体孵育的滋养层细胞中磷酸化细胞外调节蛋白激酶（ERK）的表达以及核因子 - κB（NF - κB）的DNA结合活性进行检测。
抗CagA抗体可识别细胞滋养层细胞的β - 肌动蛋白，呈现出剂量依赖性结合。用剂量递增的抗CagA抗体孵育细胞滋养层细胞，显著降低了其侵袭能力，同时导致磷酸化ERK表达显著下降以及NF - κB转位活性降低。
本研究表明，抗CagA抗体可识别细胞滋养层细胞的β - 肌动蛋白，降低其侵袭能力，这或许为上述流行病学关联提供了生物学解释。
Previous studies reported an epidemiological association between CagA-positive H. pylori strains and pre-eclampsia. As antibodies anti-CagA cross-react with endothelial cells and trophoblast cells show an endothelial phenotypic profile, we hypothesized that anti-CagA antibodies may recognize antigens of cytotrophoblast cells, thus impairing their function. Placenta samples were obtained from healthy women. Cytotrophoblast cells were cultured in a medium containing increasing concentration of polyclonal anti-CagA antibodies. Binding of anti-CagA antibodies to cytotrophoblast cells was evaluated by cell ELISA and immunofluorescence assay. Invasive potential of those cells was assessed by an invasion culture system and by measuring of MMP-2. Protein sequencing was performed on antigens precipitated by anti-CagA antibodies. Measurement of phosphorylated ERK expression and NF-kB DNA-binding activity in trophoblast cells incubated with anti-CagA or irrelevant antibodies was also performed. Anti-CagA antibodies recognized β-actin of cytotrophoblast cells, showing a dose-dependent binding. Incubation of cytotrophoblast cells with increasing doses of anti-CagA antibodies significantly reduced their invasiveness and determined a significant decrease in phosphorylated ERK expression and a reduced NF-kB translocation activity. This study shows that anti-CagA antibodies recognize β-actin of cytotrophoblast cells, reducing their invasiveness ability, possibly giving a biological explanation for the epidemiological association.