Antibodies Anti‐Caga Cross‐React with Trophoblast Cells: A Risk Factor for Pre‐Eclampsia?

Abstract

Background 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. Materials and Methods 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. Results 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. Conclusions 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.

A Dormant Microbial Component in the Development of Preeclampsia

“…(334–342)]. The odds ratio of no less than 26 in PE vs. controls when the strains can produce CagA antigens is especially striking, not least because it provides a mechanistic link to poor trophoblast invasion via a mechanism involving host antibodies to CagA cross-reacting with trophoblasts (343, 344), and circulating (345) in microparticles (346) or endosomes (347, 348). …”

Helicobacter pylori infection and extragastroduodenal diseases

“…В более позднем экспериментальном исследовании F. Franceschi и соавт. [65] показано, что антитела против CagA могут перекрестно реа-гировать с β-актином клеток цитотрофобласта, гипотетически объясняя описанную выше клиническую ассоциацию.…”

Helicobacter pylori and Perinatal Pathologies: Pathogen Transmission During Childbirth?

“…It has already been seen that H. pylori infection, as mentioned above, is associated to several pathologies during pregnancy, such as PE and RCIU that are mainly characterized by and abnormal placentation that leads to spontaneous abortion cases. In addition, it has recently been proved that anti-CagA antibodies have a cross reaction with respect to in vitro cytotrophoblast cells and they reduce their invasiveness ability [23]. In a study performed in 2011 by Hajishafiha et al [25], their inference is that when there is an infection caused by H. pylori strains that are CagA positive, there is an increase in the potential of an early abortion (possibly through the increase of inflammatory cytokins release).…”

“…It has recently been proved that anti-CagA antibodies show an in vitro cross reaction on placental tissue that in turn decreases its invasiveness ability [23]; abnormal placentation might lead to a consequent IUGR.…”

“…Hyperemesis gravidarum [8][9][10][11][12] Preeclampsia [13][14][15]23] Iron-deficiency Anemia [16][17][18][19] Intrauterine growth Restriction [20][21][22]27] Spontaneous abortion [24][25][26] and inflammatory damage over the gastric epithelium resulting in gastrointestinal disturbance such as hyperemesis gravidarum. H. pylori sequesters essential micronutrients from the host organism such as Iron (Fe) and it causes iron deficiency anemia.…”