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PROMISSE: progress in understanding pregnancy complications in patients with SLE

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 [13] (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


  1. 1.

    Girardi G, Berman J, Redecha P, Spruce L, Thurman JM, Kraus D, Hollmann TJ, Casali P, Caroll MC, Wetsel RA, Lambris JD, Holers VM, Salmon JE: Complement C5a receptors and neutrophils mediate fetal injury in the antiphophospholipid syndrome. J Clin Invest. 2003, 112: 1644-1654.

  2. 2.

    Salmon JE, Girardi G, Lockshin MD: The antiphospholipid syndrome - a disorder initiated by inflammation: implications for therapy of pregnant patients. Nat Clin Pract Rheumatol. 2007, 3: 140-147. 10.1038/ncprheum0432.

  3. 3.

    Lynch AM, Salmon JE: Dysregulated complement activation as a common pathway of injury in preeclampsia and other pregnancy complications. Placenta. 2010, 31: 561-567. 10.1016/j.placenta.2010.03.010.

  4. 4.

    Lockshin MD, Kim M, Laskin CA, Guerra M, Branch DW, Merrill J, Petri M, Porter F, Sammaritano L, Stephenson MD, Buyon J, Salmon JE: Lupus anticoagulant, but not anticardiolipin antibody, predicts adverse pregnancy outcome in patients with antiphospholipid antibodies. Arthritis Rheum. 2012, 64: 2311-2318. 10.1002/art.34402.

  5. 5.

    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.

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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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Correspondence to JE Salmon.

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Salmon, J. PROMISSE: progress in understanding pregnancy complications in patients with SLE. Arthritis Res Ther 14, A39 (2012).

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  • Systemic Lupus Erythematosus
  • Preeclampsia
  • Pregnancy Outcome
  • Complement Activation
  • Pregnancy Complication