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Antibodies Anti‐Caga Cross‐React with Trophoblast Cells: A Risk Factor for Pre‐Eclampsia?
Author(s) -
Franceschi Francesco,
Di Simone Nicoletta,
D'Ippolito Silvia,
Castellani Roberta,
Di Nicuolo Fiorella,
Gasbarrini Giovanni,
Yamaoka Yoshio,
Todros Tullia,
Scambia Giovanni,
Gasbarrini Antonio
Publication year - 2012
Publication title -
helicobacter
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.206
H-Index - 79
eISSN - 1523-5378
pISSN - 1083-4389
DOI - 10.1111/j.1523-5378.2012.00966.x
Subject(s) - cytotrophoblast , antibody , trophoblast , polyclonal antibodies , antigen , microbiology and biotechnology , biology , cell culture , placenta , immunology , genetics , pregnancy , fetus
Background Previous studies reported an epidemiological association between C ag A ‐positive H . pylori strains and pre‐eclampsia. As antibodies anti‐ C ag A cross‐react with endothelial cells and trophoblast cells show an endothelial phenotypic profile, we hypothesized that anti‐ C ag A 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‐ C ag A antibodies. Binding of anti‐ C ag A 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‐ C ag A antibodies. Measurement of phosphorylated ERK expression and NF ‐k B DNA ‐binding activity in trophoblast cells incubated with anti‐ C ag A or irrelevant antibodies was also performed. Results Anti‐ C ag A antibodies recognized β‐actin of cytotrophoblast cells, showing a dose‐dependent binding. Incubation of cytotrophoblast cells with increasing doses of anti‐ C ag A antibodies significantly reduced their invasiveness and determined a significant decrease in phosphorylated ERK expression and a reduced NF ‐k B translocation activity. Conclusions This study shows that anti‐ C ag A antibodies recognize β‐actin of cytotrophoblast cells, reducing their invasiveness ability, possibly giving a biological explanation for the epidemiological association.