Elevated Autoantibodies Linked to Preeclampsia

Women who develop preeclampsia during pregnancy are more likely to develop certain dangerous autoantibodies than women with normal pregnancies, and these autoantibodies are still present two years after childbirth in about 20 percent of women who had the disorder, scientists from the University of Pittsburgh report in the March issue of Hypertension, the journal of the American Heart Association.

Also known as toxemia, preeclampsia affects some 5 percent of pregnancies and is a leading cause of maternal and fetal illness and death, particularly in developing nations. Signs include high blood pressure, swelling of the ankles and the presence of protein in the urine. The condition typically appears after the mid-point of pregnancy. The only effective treatment is immediate delivery, which can be dangerous for the baby if it is too early. Untreated, the condition can lead to organ failure, coma and death. Preeclampsia also has been linked to an increased lifetime risk for heart disease.

"Further study is required to determine whether the presence of these autoantibodies could be an early marker for preeclampsia risk, but early data are promising," said Carl A. Hubel, Ph.D., the study's lead author and assistant professor of obstetrics, gynecology and reproductive sciences at the University of Pittsburgh School of Medicine. "Learning more about these autoantibodies also might enable us to identify a subset of women who are at greater risk for heart disease later in life, and give us a closer understanding of what causes preeclampsia."

For most women, the autoantibodies eventually go away after pregnancy. "But in some, they persist or reappear, consistent with other data showing that many of the risk factors for preeclampsia are the same as those for cardiovascular disease," added Dr. Hubel, who also is an associate investigator at the university-affiliated Magee-Womens Research Institute.

Autoantibodies are immune system proteins that attack the body's own cells instead of microorganisms that represent a real threat, such as viruses, bacteria or other toxins. Dr. Hubel and his colleagues studied the development of autoantibodies capable of activating the angiotensin II type 1 receptor (AT1-AA). The AT1 receptor is part of an amino acid group that works within cells to maintain healthy blood vessels and manage inflammation. Too much AT1 receptor activation, such as takes place when the autoantibodies are present, can lead to high blood pressure and inflammation.

"These antibodies are similar to antibodies in other conditions, such as those related to the autoimmune thyroid disorder Grave's disease," said Dr. Hubel. "These kinds of antibodies also are related to high blood pressure, which is one of the signs of preeclampsia. Women with a history of preeclampsia have a substantially higher cardiovascular risk later in life, compared to women who experienced normal pregnancies."

While the cause of preeclampsia remains unknown, evidence is mounting that the disorder relates to poor formation and placement of the placenta combined with underlying maternal factors including insulin resistance, obesity and inflammation that are magnified during the physiological stress of pregnancy.

Elevated levels of AT1-AA are evident in nearly all women with preeclampsia, the researchers report. Blood samples from 29 women with preeclampsia and 35 women who had normal pregnancies at Magee-Womens Hospital of UPMC in Pittsburgh and Massachusetts General Hospital in Boston were studied. The samples were collected between six months and two years postpartum to allow for stabilization of normal, pregnancy-induced cardiovascular changes.

"AT1-AA were detected in 17.2 percent of postpartum women who had developed preeclampsia, as opposed to 2.9 percent of postpartum women whose pregnancies were uncomplicated," said Dr. Hubel.

In addition to Dr. Hubel, study authors are Gerd Wallukat, Ph.D., Max Delbruck Center for Molecular Medicine, Berlin; Myles Wolf, M.D., and Ravi Thadhani, M.D., both of Massachusetts General Hospital; Augustine Rajakumar, Ph.D., James M. Roberts, M.D., and Nina Markovic, Ph.D., all of the University of Pittsburgh and Magee-Womens Research Institute; and Florian Herse, M.D., Friedrich C. Luft, M.D., and Ralf Dechend, M.D., of the Franz Volhard Clinic, Berlin.

Funding for the study was provided by the Massachusetts Institute of Technology, Magee-Womens Hospital of UPMC, the National Institutes of Health and the American Heart Association.