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Study Identifies Biomarker Linked to Poor Outcomes in Pregnant Lupus Patients

San Diego—October 27, 2013

Researchers at Hospital for Special Surgery in New York City have identified a biomarker that may predict poor pregnancy outcomes in lupus patients.

The study, titled “Angiogenic Factor Dysregulation and Risk of Adverse Pregnancy Outcome In Lupus Pregnancies” was presented at the American College of Rheumatology/Association of Rheumatology Health Professionals Annual Meeting on October 27 in San Diego.

Investigators found that an imbalance of angiogenic factors, proteins required for the development of the placenta and the health of blood vessels, is associated with poor pregnancy outcomes. Increased levels of an anti-angiogenic protein called sFlt1 in pregnant lupus patients placed them at increased risk of placental insufficiency and preeclampsia, a potentially life-threatening complication. Scientists determined that higher levels of sFlt1 reduce the activity of other angiogenic proteins (placental growth factor, PIGF; vascular endothelial growth factor, VEGF) that are necessary for growth of the placenta and the mother’s blood vessels.

“Pregnant women with lupus or antiphospholipid syndrome are at increased risk for adverse outcomes, particularly preeclampsia, yet identification of those destined for complications has been elusive,” said Jane Salmon, MD, director of the Lupus and APS Center of Excellence at Hospital for Special Surgery and lead author of the study. “We prospectively studied patients to see if we could find a biomarker early in pregnancy that would predict a poor outcome.”

The study is part of an ongoing, multi-center research initiative led by Dr. Salmon known as PROMISSE (Predictors of pRegnancy Outcome: bioMarkers In antiphospholipid antibody Syndrome and Systemic lupus Erythematosus) funded by the National Institutes of Health to identify factors that predict pregnancy complications in women with lupus and antiphospholipid syndrome.

Lupus is a chronic inflammatory disease in which the body’s own immune system attacks tissues of the body and can cause complications during pregnancy. Preeclampsia, which is characterized by the onset of high blood pressure and impaired kidney function, is life-threatening to both mother and baby.

Scientists enrolled 384 pregnant women with lupus and 153 healthy pregnant controls.

Subjects were evaluated and blood was drawn monthly beginning 12 weeks into their pregnancy. Poor pregnancy outcomes were defined as preeclampsia, fetal death, neonatal death, preterm delivery before 36 weeks because of placental insufficiency, or intrauterine growth restriction (IUGR), which refers to a poor growth rate of the baby while in the womb. Levels of sFlt1 and other angiogenic proteins were measured and compared in women with lupus versus controls.

In the study, 20 percent of pregnant lupus patients developed preeclampsia or another poor outcome. Levels of sFlt1 protein, an anti-angiogenic factor, were significantly higher in patients destined for complications compared to lupus patients whose pregnancies were uncomplicated.  In contrast, levels of PlGF, an angiogenic factor, were lower.  Alteration in the balance of angiogenic factors was evident as early as 12 to 15 weeks into the pregnancy and persisted throughout pregnancy in women who experienced preeclampsia or another complication.

“Measurement of sFlt1 and PlGF provide a powerful tool to identify pregnant lupus patients at high risk for poor pregnancy outcomes sufficiently early to intervene,” Dr. Salmon said.  “Hopefully, this will facilitate trials of novel treatments to prevent these devastating complications.”

 

About HSS | Hospital for Special Surgery
HSS is the world’s leading academic medical center focused on musculoskeletal health. At its core is Hospital for Special Surgery, nationally ranked No. 1 in orthopedics (for the ninth consecutive year) and No. 3 in rheumatology by U.S.News & World Report (2018-2019). Founded in 1863, the Hospital has one of the lowest infection rates in the country and was the first in New York State to receive Magnet Recognition for Excellence in Nursing Service from the American Nurses Credentialing Center four consecutive times. The global standard total knee replacement was developed at HSS in 1969. An affiliate of Weill Cornell Medical College, HSS has a main campus in New York City and facilities in New Jersey, Connecticut and in the Long Island and Westchester County regions of New York State. In 2017 HSS provided care to 135,000 patients and performed more than 32,000 surgical procedures. People from all 50 U.S. states and 80 countries travelled to receive care at HSS. In addition to patient care, HSS leads the field in research, innovation and education. The HSS Research Institute comprises 20 laboratories and 300 staff members focused on leading the advancement of musculoskeletal health through prevention of degeneration, tissue repair and tissue regeneration. The HSS Global Innovation Institute was formed in 2016 to realize the potential of new drugs, therapeutics and devices. The culture of innovation is accelerating at HSS as 130 new idea submissions were made to the Global Innovation Institute in 2017 (almost 3x the submissions in 2015). The HSS Education Institute is the world’s leading provider of education on the topic on musculoskeletal health, with its online learning platform offering more than 600 courses to more than 21,000 medical professional members worldwide. Through HSS Global Ventures, the institution is collaborating with medical centers and other organizations to advance the quality and value of musculoskeletal care and to make world-class HSS care more widely accessible nationally and internationally.

 

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