Theodore E. Woodward Award: antiphospholipid syndrome revisited: a disorder initiated by inflammation.
The antiphospholipid syndrome (APS), characterized by thrombosis and pregnancy loss that occur in the presence of antiphospholipid (aPL) antibodies, is a leading cause of miscarriage and maternal and fetal morbidity. Using a mouse model of APS induced by passive transfer of human aPL antibodies, we have shown that complement activation plays an essential and causative role in pregnancy loss and fetal growth restriction, and that blocking activation of the complement cascade rescues pregnancies. Given that the primary treatment for APS patients is anticoagulation throughout pregnancy, usually with sub-anticoagulant doses of heparin, we considered the possibility that heparin prevents pregnancy loss by inhibiting complement. We found that heparin inhibits activation of complement on trophoblasts in vivo and in vitro and that anticoagulation, in and of itself, is not sufficient to prevent pregnancy complications in our experimental model of APS. Our studies underscore the importance of inflammation in fetal injury associated with aPL antibodies and emphasize the importance of developing and testing targeted complement inhibitory therapy for patients with APS.
Department of Medicine, Weill Medical College of Cornell University, New York, NY 10021, USA. salmonj@hss.edu
Jane E
JE
Salmon
Guillermina
G
Girardi
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D016736:Antiphospholipid Syndrome / Q000150:complications / Q000188:drug therapy / Q000209:etiology* / Q000276:immunology; D001363:Awards and Prizes; D015510:Clinical Medicine; D003167:Complement Activation; D051056:Complement Inactivating Agents / Q000494:pharmacology; D005260:Female; D005313:Fetal Death / Q000209:etiology / Q000276:immunology; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D007108:Immune Tolerance; D007249:Inflammation / Q000150:complications* / Q000276:immunology; D008431:Maternal-Fetal Exchange / Q000276:immunology; D051379:Mice; D008954:Models, Biological; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy / Q000209:etiology / Q000276:immunology; D012958:Societies, Scientific; D014481:United States
D000925:Anticoagulants; D051056:Complement Inactivating Agents; D006493:Heparin