BOSTON, Massachusetts—Measuring levels of circulating antiangiogenic factors—soluble fms-like tyrosine kinase 1 (sFlt 1) and soluble endoglin (sEng)—may help identify which patients with systemic lupus erythematosus (SLE) and/or antiphospholipid antibodies (APLA) will develop preeclampsia. The researchers suggest that an angiogenic imbalance early in pregnancy increases the vulnerability to triggers of preeclampsia, according to data from the PROMISSE Study (Predictors of pRegnancy Outcome: bioMarkers In antiphospholipid antibody Syndrome and Systemic lupus Erythematosus) presented at the American College of Rheumatology meeting in Boston.

"These findings indicate that circulating antiangiogenic factors are early markers predictive of preeclampsia in patients with SLE," said lead researcher Jane E. Salmon, MD. Dr. Salmon is the Collette Kean Research chair and the co-director of the Kirkland Center for Lupus Research, Hospital for Special Surgery in New York City. "Because inflammatory mediators trigger production of antiangiogenic factors, early intervention to block specific pathways of inflammation could prevent angiogenic imbalance in lupus pregnancies at risk for preeclampsia."

In the absence of any interventions, "it is difficult to know what to do with the data," Dr. Salmon told MSKReport.com.

A total of 211 women with SLE and/or APLA and who were <12 weeks pregnant were followed through pregnancy. Sixteen patients with SLE and/or increased APLA who developed preeclampsia were matched based on age and ethnicity to another SLE+ and/or APLA+ patient who did not develop preeclampsia and a nonautoimmune patient who had an uncomplicated pregnancy.

By weeks 12 to 15, researchers started to see elevations in these antiangiogenic factors in patients with lupus and/or APLA. "Certainly by week 20 to 23, there was a significant difference between patients who will have preeclampsia and those who will not based on these elevations," Dr. Salmon said.

The slope of the increase in circulating antiangiogenic factors through pregnancy was significantly higher in the SLE+ and/or APLA+ patients who went on to develop preeclampsia, and it was higher in participants with SLE and/or APLA compared with nonautoimmune participants who had healthy pregnancies. Specifically, as early as 12 to 15 weeks' gestation, levels of circulating sFlt-1 were higher in SLE+ and/or APLA+ patients compared with controls (P = .08). The rate of increase in sFlt-1 through pregnancy was significantly higher in patients who went on to develop preeclampsia compared with those who did not (P = .0019). Moreover, levels of sFlt-1 were higher in people with lupus who did not develop preeclampsia compared with healthy controls (P = .0002).

Study patients with SLE or APLA with elevated levels of sFlt-1 at 20 to 23 weeks' gestation were at increased risk for preeclampsia later in pregnancy (P = .05). Similarly, patients with increased sEng levels at 20 to 23 weeks were at higher risk for preeclampsia (P = .005).
 
Ratio helps predict risk

"We can develop a ratio of angiogenic and antiangiogenic factors to help predict risk," Dr. Salmon commented. "The goal is to identify biomarkers and then develop therapies to block critical inflammatory pathways and ultimately do intervention studies, which will be unbelievably important."

The new findings have implications for preeclampsia risk in the general population as well. "If preeclampsia is a disease triggered by placental inflammation and if we understand what drives this inflammation in the placenta of patients with lupus, we may be able to translate it to patients at risk of preeclampsia who do not have lupus," Dr. Salmon ended.

Daniel H. Solomon, MD, MPH, an associate physician at Brigham and Women's Hospital in Boston said that the new findings "highlight some important biomarkers to help predict which patients with lupus may go on to develop complications in the placenta leading to preeclampsia."


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