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Lupus Research Update: 2008 Volume 1

Volume 1, 2008 - Online Edition | In This Issue


ALR Funded International Consortium Identifies Genes Linked to Lupus >
The Faces of Lupus: Eddie Kennison, Kansas City Chiefs >
Meet the Investigator — Mary K. Crow, M.D., Named Chair of Scientific Advisory Board >
Research Results — A New Clue in the Survival of Autoimmune B Cells >
Research Results — Narrowing Down a Lupus-Related Gene >
Research Results — Finding Hidden Clues to Children's Lupus Nephritis >
Research Results — Finding Ways to a Safer Pregnancy for Women with Lupus >
Drug Research and Development News >
Leaving a Legacy >

Research Results — Finding Ways to a Safer Pregnancy for Women with Lupus

One of the cruelest facts about lupus is that it tends to strike young women in the prime of their reproductive years. And while women with lupus can have normal pregnancies and deliver healthy babies, they have a higher risk of complications, including preeclampsia, fetal growth restriction and miscarriage. The risks are highest in women who also have antiphospholipid antibodies, which cause vascular inflammation and increase the likelihood of blood clots.

Preeclampsia is associated with insufficient blood flow in the placenta and abnormal development of the placenta. It is a major cause of maternal, fetal and neonatal complications and deaths. In preeclampsia, the presence of anti-angiogenic proteins in the mother's circulation prevents the growth of blood vessels in the placenta and injures the mother's kidneys and blood vessels. The mother also experiences high blood pressure and protein in the urine, swelling, weight gain, headaches and, eventually, seizures. The fetus does not grow properly and is often born severely prematurely.

To identify approaches to reduce the risk of preeclampsia and other complications in pregnant women with lupus, the National Institutes of Health has funded a multicenter study called PROMISSE (Predictors of pRegnancy Outcome: biomarkers In antiphospholipid Syndrome and Systemic lupus Erythematosus). A lead researcher in the project is former ALR grantee Jane E. Salmon, M.D., of the Hospital for Special Surgery in New York City.

In November, Dr. Salmon presented data from her work at the American College of Rheumatology's annual scientific meeting in Boston showing that measuring levels of antiangiogenic factors in the mother's circulation could help predict which women would develop preeclampsia. The ALR supported her work in animal models of lupus pregnancy, which led to the current study.

She and her team, which included ALR grantee Jill Buyon, M.D., compared anti-angiogenic levels in 211 women with lupus or antiphospholipid syndrome (APS), some of whom developed preeclampsia and some of whom had normal pregnancies, with healthy pregnant women without the diseases. As early as 12 to 15 weeks into the pregnancy, the researchers noticed that levels of circulating anti-angiogenic factors were significantly higher in women who went on to develop preeclampsia.

Although there is currently no treatment for preeclampsia, simply knowing which women are more likely to develop it would enable physicians to keep a closer watch on these women throughout their pregnancies to try and minimize its effects on mother and baby.

The goal, of course, is to find a way to prevent preeclampsia in the first place. To that end, Dr. Salmon is investigating the mediators that lead to the production of these antiangiogenic factors. Her work in experimental models suggests that inflammation damages the placenta and triggers production of anti-angiogenic factors. If the link truly exists, then interventions to block specific pathways of inflammation could prevent the production of anti-angiogenic factors, in turn preventing angiogenic imbalance in lupus pregnancies and reducing the overall risk of preeclampsia.

In the meantime, however, Dr. Salmon stresses that with proper care, close supervision and appropriate planning for pregnancy (i.e., when the disease is inactive), women with lupus can deliver healthy babies. That's a far cry from the 1960s and 70s, when women with lupus were counseled not to get pregnant at all. "We show that if you get pregnant at the right time, you can have a completely uncomplicated pregnancy, do very well and have a healthy baby," said Dr. Salmon.

Salmon, JE, Guerra M, Kim M, et al. Elevated antiangiogenic factors predict preeclampsia in pregnant patients with SLE and/or APL antibodies. Presented at: American College of Rheumatology Meeting; November 6-11, 2007; Boston, Mass. Presentation L9.

Just the Facts

What the study showed:
High levels of antiangiogenic factors can help predict which women with lupus will develop preeclampsia during their pregnancy.

What it means:
These biomarkers provide an early warning sign of a serious risk to pregnant women, enabling doctors to intervene earlier. Targeting this complication may enable more women with lupus to deliver healthy babies. What's next: Identifying the biochemical process that leads to the production of these factors and arresting it early on, before high levels can be produced that lead to preeclampsia.

ALR funding:
$1.5 million


1.5 million

people in the U.S. have Lupus.

90 million

dollars committed to lupus research by the Alliance for Lupus Research.


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