Guillermina Girardi, PhD

Appointments

Associate Scientist, Hospital for Special Surgery

Assistant Professor, Weill Medical College of Cornell University

 

Selected Publications

Redecha, P; Tilley, R; Tencati, M; Salmon, JE; Kirchhofer, D; Mackman, N; Girardi, G. Tissue factor: a link between C5a and neutrophil activation in ntiphospholipid antibody-induced fetal injury. Blood 2007;110(7):2423-31. Inside Blood commentary by K McRae.

Girardi, G. Guilty as charged: all available evidence implicates complement's role in fetal demise. Am J Reprod Immunol 2008; 59(3):183-92.

Girardi, G. Complement inhibition keeps mother calm and avoids fetal rejection. Immunol Invest. 2008;37(5):645-59.

Girardi, G; Mackman, N. Tissue factor in antiphospholipid antibody-induced pregnancy loss: a pro-inflammatory molecule. Special issue of LUPUS: “Mechanisms of thrombosis in autoimmune diseases.” Lupus (2008) 17, 932-937.

Redecha, P; Franzke,C; Ruf, W; Mackman, N; Girardi, G. Activation of Neutrophils by the Tissue Factor - Factor VIIa - PAR-2 Axis Mediates Fetal Death in Antiphospholipid Syndrome. J Clin Invest. 2008;118(10):3453-61.Commentary by H Weiler.

Girardi, G. Pravastatin prevents miscarriages in antiphospholipid antibody-treated mice. J Reprod Immunol 2009, in press.

Redecha, P; van Rooijen, N; Torry, D; Girardi, G. Pravastatin prevents miscarriages in mice: Role of tissue factor in placental and fetal injury. Blood, in press 2009.

For more publications, please see the PubMed listing.  

Research Description

Immune Mediated Placental and Vascular Injury

The antiphospholipid syndrome, characterized by thrombosis and pregnancy loss that occur in the presence of antiphospholipid antibodies, is a leading cause of miscarriage and maternal and fetal morbidity. In addition to recurrent miscarriage, preeclampsia, placental insufficiency, and intrauterine growth restriction are found in about 20% of pregnancies in women with aPL antibodies. Fetal growth restriction is the second leading cause of perinatal morbidity and mortality, followed only by prematurity. Despite considerable research, the cause or causes of aPL antibody-induced pregnancy complications remain unclear and there are no clinically useful screening tests to identify women in whom they will develop.

We have identified a previously unrecognized role for complement as an early effector in pregnancy loss associated with placental inflammation. In addition, we have shown that treatment with heparin, the standard therapy for pregnant patients with antiphospholipid syndrome, prevents complement activation and protects mice from pregnancy complications induced by antiphospholipid antibodies, and that anticoagulants that do not inhibit complement do not protect pregnancies.

Our goal is to understand the causes of antiphospholipid antibody-induced pregnancy complications and other causes of immune mediated pregnancy loss. The maternal-placental-fetal units act in harmony to provide the needs of the fetus while supporting the physiologic changes of the mother. It is recognized that placental vascular insufficiency is a core feature in abnormal pregnancies. Placental development requires adequate and organized interaction of vascular growth factors and their receptors. Failure in the angiogenesis process may result in the defective placental development. Women with thrombophilia have an increased risk of pregnancy loss and other serious obstetric complications. Endothelial vessels damage and thrombosis induced by antiphospholipid antibodies may also mediate fetal and placental damage. Our efforts are aimed at understanding the role of complement, thrombosis and angiogenesis as possible mediators of fetal and placental damage.

Identification of the mediators responsible for pregnancy loss and intrauterine growth restriction is likely to help diagnosis, prevention and therapy. Timely diagnosis and management of pregnancy complications can result in a favorable outcome, reducing fetal and maternal morbidity and mortality.