Updating on the pathogenic mechanisms 5 of the antiphospholipid antibodies-associated pregnancy loss.
Anti-phospholipid antibodies (aPL) are risk factor for recurrent pregnancy loss and obstetrical complications. The mechanisms of aPL-mediated pregnancy failure are still a matter of research. Although aPL are associated with thrombosis, thrombotic events cannot explain all the miscarriages. There is evidence for a direct in vitro aPL effect on the trophoblast as shown by their binding; reduction of proliferation, human chorionic gonadotrophin release, in vitro invasiveness, adhesion molecule expression; and increased apoptosis. Such a direct reactivity is supported by the expression of beta2 glycoprotein (beta 2GP) I on trophoblast cell membranes. aPL/anti-beta 2GPI antibodies also bind to human decidual/endometrial cells in vitro and induce a pro-inflammatory phenotype. APL-mediated inflammatory processes at the placental level are apparently responsible for fetal loss at least in animal models. Both complement activation and pro-inflammatory cytokine/chemokine secretion have been shown to play a role. More recently, complement-induced tissue factor expression on infiltrating neutrophils was described as an additional pathogenic mechanisms mediated by aPL. As a whole, these findings do suggest that aPL may induce a defective placentation by acting at different levels without involving necessarily thrombotic events.
Meroni
Pier Luigi
PL
Department of Internal Medicine, University of Milan, Milan, Italy. pierluigi.meroni@unimi.it
Gerosa
Maria
M
Raschi
Elena
E
Scurati
Silvia
S
Grossi
Claudia
C
Borghi
Maria O
MO
D000026:Abortion, Habitual / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D017152:Antibodies, Antiphospholipid / Q000276:immunology*; D016736:Antiphospholipid Syndrome / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D001323:Autoantibodies / Q000276:immunology* / Q000378:metabolism; D003656:Decidua / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D010929:Placentation; D011247:Pregnancy; D011248:Pregnancy Complications / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D013927:Thrombosis / Q000276:immunology / Q000503:physiopathology; D014327:Trophoblasts / Q000276:immunology / Q000378:metabolism; D053482:beta 2-Glycoprotein I / Q000276:immunology / Q000378:metabolism*
D017152:Antibodies, Antiphospholipid; D001323:Autoantibodies; D053482:beta 2-Glycoprotein I