PROMISSE: progress in understanding pregnancy complications in patients with SLE

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 [1-3] (Figure 1). The PROMISSE Study (Predictors of Pregnancy Outcome: Biomarkers in Antiphospholipid Antibody Syndrome and Systemic Lupus Erythematosus) is a first-time effort to translate (Figure Presented) our novel findings in mice to humans and determine examine the role of complement as a mediator of complications in patients with antiphospholipid (aPL) antibodies and/or SLE. The following discoveries from PROMISSE will be summarized: lupus anticoagulant is the most powerful predictor of poor pregnancy outcomes in aPL-positive patients [4]; activation of complement early in pregnancy can be detected in the blood of women destined to have preeclampsia; circulating antiangiogenic factors are biomarkers that predict preeclampsia in patients with SLE and/or aPL antibodies and can be released by products of complement activation; and mutations in complement pathway genes that lead to uncontrolled complement activation are associated with preeclampsia in pregnant patients with SLE and/or aPL antibodies [5]. These findings bring us to closer to identifying those at highest risk for pregnancy complications and intervening to block pathways of injury, such as complement.