The PROMISSE Study is an observational study of 700 pregnant patients, enrolled at nine major clinical centers. The purpose of the study is 1) to determine whether certain proteins (called complement split products) that can injure healthy organs can be used to predict poor pregnancy outcome in patients with systemic lupus erythematosus (SLE) and anti-phospholipid syndrome (APS), and/or 2) to determine whether elevated levels of circulating antiangiogenic factors predict pregnancy complications in patients with aPL antibodies and/or SLE.

Thrombosis and pregnancy loss are common features of systemic lupus erythematosus (SLE), particularly in the presence of antiphospholipid (aPL) antibodies. The in vivo mechanisms by which aPL antibodies lead to vascular events and, specifically, to recurrent fetal loss are largely unknown. Studies in a mouse model of antiphospholipid antibody syndrome (APS) indicate that in vivo complement activation is necessary for fetal loss caused by aPL antibodies. This study represents an effort to translate these research observations on the potential role of complement activation in the pathogenesis of aPL antibody-mediated pregnancy loss to a clinically relevant human study.

In addition, studies in humans and mice have shown 1) that the balance of circulating angiogenic and antiangiogenic factors predicts preeclampsia and fetal growth restriction in healthy women, 2) circulating antiangiogenic factors cause endothelial dysfunction and abnormal placental development in animal models, and 3) complement activation leads to elevated levels of circulating antiangiogenic factors and complement inhibition prevents increased levels of antiangiogenic factors, placental dysfunction and fetal growth restriction in a mouse model of APS. This study will permit testing the hypothesis that, like in healthy women, the balance of circulating angiogenic and antiangiogenic factors predict complications in women with SLE and APS and to translate the findings in animal models into humans.

The PROMISSE Study is a prospective observational study that will follow 700 pregnant patients who will be grouped and analyzed according to the presence or absence of aPL antibodies and preexisting SLE. The patients are followed regularly during the course of the pregnancy, collecting medical and obstetrical information as well as serial blood specimens for complement and cytokine assays. The data obtained will be analyzed and used to identify mechanisms and predictors of poor fetal outcome. We expect that the insights provided through this study will suggest means to prevent, arrest or modify these conditions.

Inclusion Criteria:

• Patient pregnant with live intrauterine pregnancy, as defined by positive test for elevated β-HCG, but ≤ 12 weeks by gestation (for subjects without aPL antibodies) and ≤18 weeks (for subjects with aPL antibodies)

• Patient between the ages of 18-45 and able to give informed consent, or age < 18 years with parental consent

• Hematocrit > 26%

• For APL positive:

  • aCL: IgG >= 40 GPL units; IgM >= 40 MPL units
  • Positive LAC (RVVT, Kaolin, dilute TTI or PTT LA)
  • Anti-β2GPI: IgG >= 40 GPL units; IgM >= 40 MPL units

• For control subjects:

  • At least one successful pregnancy
  • No history of fetal death (death of conceptus ≥ 10 weeks' gestation)
  • No more than 1 miscarriage < 10 weeks' gestation
  • No history of positive aPL in local lab or positive aPL in core labs at screening
  • Not currently a smoker
  • No medical problems requiring chronic treatment

Exclusion Criteria:

• Diabetes mellitus (Type I and Type II) antedating pregnancy
• Known or suspected hereditary complement deficiency (defined by CH50 = 0)

Pregnant patients identified by investigators at each study site

Because the investigative team is still analyzing the data for biomarkers and genetics, the authors are not willing to make the data public at this time. Published study results can be found under Publications on the ClinicalTrials.gov site for this study.