Antiphospholipid antibodies affect trophoblast gonadotropin secretion and invasiveness by binding directly and through adhered beta2-glycoprotein I.
OBJECTIVE
To investigate the in vitro ability of antiphospholipid antibodies (aPL) to bind human trophoblast cells and to affect gonadotropin secretion and invasiveness.


METHODS
Antiphospholipid antibody IgG from women with recurrent miscarriages, beta2-glycoprotein I (beta2GPI)-independent IgG aPL human monoclonal antibody (mAb) (519), and IgM anti-beta2GPI human mAb (TMIG2) were investigated for their binding to trophoblasts cultured for various amounts of time, their ability to affect invasiveness of Matrigel-coated filters, and their release of human chorionic gonadotropin (hCG).


RESULTS
Polyclonal IgG aPL, as well as mAb 519 and TMIG2, bound to trophoblasts, the highest binding being found when cells displayed the greatest amount of syncytium formation. TM1G2 binding was found to be betaGPI dependent. Both polyclonal and monoclonal aPL, but not the controls, significantly reduced hCG release and Matrigel invasiveness.


CONCLUSIONS
These findings suggest that aPL recognition of both anionic PL and adhered beta2GPI on trophoblast cell structures might represent a potential pathogenetic mechanism for defective placentation in women with the antiphospholipid syndrome.
Di Simone
N
N
Universita' Cattolica del S. Cuore, Rome, Italy.
Meroni
P L
PL
de Papa
N
N
Raschi
E
E
Caliandro
D
D
De Carolis
C S
CS
Khamashta
M A
MA
Atsumi
T
T
Hughes
G R
GR
Balestrieri
G
G
Tincani
A
A
Casali
P
P
Caruso
A
A
D000838:Anions / Q000276:immunology / Q000378:metabolism; D017153:Antibodies, Anticardiolipin / Q000097:blood / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D016736:Antiphospholipid Syndrome / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D006063:Chorionic Gonadotropin / Q000378:metabolism*; D005260:Female; D006023:Glycoproteins / Q000276:immunology*; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000494:pharmacology; D066298:In Vitro Techniques; D011247:Pregnancy; D011248:Pregnancy Complications / Q000276:immunology; D011485:Protein Binding / Q000276:immunology; D014327:Trophoblasts / Q000276:immunology* / Q000378:metabolism*; D053482:beta 2-Glycoprotein I
D000838:Anions; D017153:Antibodies, Anticardiolipin; D000911:Antibodies, Monoclonal; D006063:Chorionic Gonadotropin; D006023:Glycoproteins; D007074:Immunoglobulin G; D053482:beta 2-Glycoprotein I; D007987:Gonadotropin-Releasing Hormone