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 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 anti-angiogenic 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.
Figure 1.
Acknowledgements
This work is presented on behalf of the PROMISSE Investigators (J Buyon, M Kim, MD Lockshin, CA Laskin, DW Branch, J Merrill, M Petri, L Sammaritano, M Stephenson) and the PROMISSE Collaborators (JP Atkinson, M Triebwasser, SA Karumanchi). This research is supported by grant NIH/NIAMS RO1 AR49772.
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