Antiphospholipid antibodies as cause of pregnancy loss.
Antiphospholipid antibodies detected by lupus anticoagulant, anticardiolipin or anti-beta2 glycoprotein I assays were associated with fetal loss. Rather than being diagnostic tools only, antiphospholipid antibodies are thought to be pathogenic. The strongest demonstration of their pathogenic role lies in the ability to induce fetal resorptions--the experimental equivalents of the human fetal losses--when passively infused in pregnant naive animals. However, still debated is how the antibodies might induce the obstetrical manifestations. Thrombotic events at the placental levels might be related to endothelial cell activation, inhibition of protein C/S system and fibrinolysis as well as to Annexin V displacement. However, the thrombophilic state apparently cannot explain all the miscarriages and a direct antibody-mediated damage on the trophoblast has been suggested. During differentiation to syncytium, trophoblasts express cell membrane anionic phospholipids that can bind beta2 glycoprotein I, the main cationic phospholipid binding protein recognized by the antiphospholipid antibodies. Adhered beta2-glycoprotein I might be recognized by the antibodies that, once bound, strongly interfere with in vitro trophoblast cell maturation so resulting in a defective placentation. These mechanisms have been suggested to play a role in early fetal loss, while thrombotic events would be responsible for miscarriages late in the pregnancy.
Allergy, Clinical Immunology and Rheumatology Unit, IRCCS Istituto Auxologico Italiano, Department of Internal Medicine, University of Milan, Milan, Italy. pierluigi.meroni@unimi.it
P L
PL
Meroni
N
N
di Simone
C
C
Testoni
M
M
D'Asta
B
B
Acaia
A
A
Caruso
D000026:Abortion, Habitual / Q000276:immunology*; D000818:Animals; D017152:Antibodies, Antiphospholipid / Q000276:immunology*; D016736:Antiphospholipid Syndrome / Q000276:immunology*; D005260:Female; D006023:Glycoproteins / Q000276:immunology; D006801:Humans; D021041:Placental Circulation; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic / Q000276:immunology; D013927:Thrombosis / Q000276:immunology; D053482:beta 2-Glycoprotein I
D017152:Antibodies, Antiphospholipid; D006023:Glycoproteins; D053482:beta 2-Glycoprotein I