- Meeting abstract
- Open Access
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.
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.
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.
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.
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.
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.
About this article
Cite this article
Salmon, J. PROMISSE: progress in understanding pregnancy complications in patients with SLE. Arthritis Res Ther 14, A39 (2012) doi:10.1186/ar3973
- Systemic Lupus Erythematosus
- Pregnancy Outcome
- Complement Activation
- Pregnancy Complication