Antibodies anti-CagA cross-react with trophoblast cells: a risk factor for pre-eclampsia?
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.


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.
Emergency Department, Catholic University of the Sacred Heart, Rome, Italy. francesco.franceschi@rm.unicatt.it
Francesco
F
Franceschi
Nicoletta
N
Di Simone
Silvia
S
D'Ippolito
Roberta
R
Castellani
Fiorella
F
Di Nicuolo
Giovanni
G
Gasbarrini
Yoshio
Y
Yamaoka
Tullia
T
Todros
Giovanni
G
Scambia
Antonio
A
Gasbarrini
D000199:Actins / Q000276:immunology*; D000907:Antibodies, Bacterial / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D002478:Cells, Cultured; D003429:Cross Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D011225:Pre-Eclampsia / Q000209:etiology*; D011247:Pregnancy; D012307:Risk Factors; D014327:Trophoblasts / Q000276:immunology*
D000199:Actins; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C080866:cagA protein, Helicobacter pylori