Antiphospholipid antibodies prevent extravillous trophoblast differentiation.
OBJECTIVE
We investigated the hypothesis that antiphospholipid antibodies (aPL) have a detrimental effect on human extravillous trophoblast (EVT) differentiation into giant multinucleated cells "in vitro."


METHODS
The EVT were isolated from the placental chorion using enzymatic digestion and Percoll gradient centrifugation. After 24, 36, and 48 hours in culture, giant multinuclear cells (GMC) were identified by immunohistochemistry using antibodies to cytokeratin 7 and counted.


METHODS
An academic research laboratory.


METHODS
Placentas were donated by women having an elective cesarean section for a normal pregnancy at term.


METHODS
This model was then used to investigate the effect of two different monoclonal aPL to beta2-glycoprotein 1 (IIC5 and ID2), and control mouse IgG antibody on EVT differentiation.


RESULTS
Freshly isolated EVT were nonproliferative but moved together losing their intervening cell walls and differentiated into GMC. Maximal numbers of GMC were detected after 48 hours of culture. The aPL, IIC5, and ID2 significantly inhibited GMC formation, whereas the mouse IgG control had no effect.


CONCLUSIONS
Antiphospholipid antibodies can inhibit EVT differentiation and GMC formation "in vitro" suggesting that a failure of trophoblast differentiation and subsequent uteroplacental development may be an underlying pathology in antiphospholipid syndrome-associated pregnancy loss.
Quenby
Siobhan
S
Department of Obstetrics and Gynaecology, Liverpool Women's Hospital, University of Liverpool, Liverpool, United Kingdom. squenby@liv.ac.uk
Mountfield
Steve
S
Cartwright
Judith E
JE
Whitley
Guy StJ
GS
Chamley
Larry
L
Vince
Gill
G
D017152:Antibodies, Antiphospholipid / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D015726:Giant Cells / Q000166:cytology / Q000276:immunology; D006801:Humans; D011247:Pregnancy; D011248:Pregnancy Complications / Q000276:immunology / Q000473:pathology; D014327:Trophoblasts / Q000166:cytology* / Q000276:immunology*
D017152:Antibodies, Antiphospholipid; D000911:Antibodies, Monoclonal