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PROMISSE: progress in understanding pregnancy complications in patients with SLE
Arthritis Research & Therapy volume 14, Article number: A39 (2012)
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 ; 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 . 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.
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Salmon JE, Heuser C, Triebwasser M, Liszewski KM, Kavanagh D, Roumenina L, Branch DW, Goodship T, Fremeaux-Bacchi V, Atkinson JP: Mutations in complement regulatory proteins predispose to preeclampsia. PLoS Med. 2011, 8: e1001013-10.1371/journal.pmed.1001013.
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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Salmon, J. PROMISSE: progress in understanding pregnancy complications in patients with SLE. Arthritis Res Ther 14, A39 (2012). https://doi.org/10.1186/ar3973
- Systemic Lupus Erythematosus
- Pregnancy Outcome
- Complement Activation
- Pregnancy Complication