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SP0011 Complement Activation and Antiphospholipid Syndrome
  1. J. Salmon1
  1. 1Rheumatology, Hospital for Special Surgery, New York, NY, United States

Abstract

Pregnancy complications in women with the antiphospholipid syndrome (APS) and/or SLE include recurrent miscarriage, preeclampsia, placental insufficiency, and intrauterine growth restriction (IUGR). The mechanisms leading to placental and fetal injury in vivo are incompletely understood and treatment remains sub-optimal. We have identified complement as an early effector in pregnancy loss and/or IUGR associated with placental inflammation in a mouse model of APS and shown that complement activation drives angiogenic imbalance, placental insufficiency and endothelial injury. In vivo murine studies also implicate activation of the classical complement pathway in thrombosis associated with APS. Activation of complement by antiphospholipid(aPL) autoantibodies generates C5a, which binds and activates neutrophils and endothelial cells. On the basis of murine studies, C3 and C5 have been proposed as possible therapeutic targets for treating obstetrical APS syndrome and case reports document the use of the C5 inhibitor eculizumab in patients with acute catastrophic APS.

The PROMISSE Study (Predictors of pRegnancy Outcome: bioMarkers In antiphospholipid antibody Syndrome and Systemic lupus Erythematosus) is a first-time effort to translate our novel findings in mice to humans and determine examine the role of complement as a mediator of complications in patients with aPL antibodies and/or SLE. The following discoveries from PROMISSE will be summarized (1) Activation of complement early in pregnancy can be detected in the blood of women destined to have preeclampsia and (2) Mutations in complement pathway genes that lead to uncontrolled complement activation are associated with preeclampsia in pregnant patients with SLE and/or aPL antibodies.

Disclosure of Interest J. Salmon Grant/research support from: Hoffmann La Roche, Consultant for: Alexion, Novartis

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