Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement

The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.


Angiogenic Factor Imbalance in Pregnant SLE Patients May Explain Increased Risk for Complications

Salmon1,  Jane E., Kim2,  Mimi Y., Rana3,  Sarosh, Guerra1,  Marta, Lockshin1,  Michael D., Branch4,  D. Ware, Laskin5,  Carl A.

Hospital for Special Surgery, New York, NY,
Albert Einstein Coll Medicine, Bronx, NY,
Beth Israel Deaconess Med Ctr, Boston, MA,
Univ of Utah, Salt Lake City, UT,
Mt. Sinai Hosp, Toronto, ON,
Johns Hopkins Univ, Baltimore, MD,
Oklahoma Med Res Found, Oklahoma City, OK,
NYU School of Medicine, New York, NY

Purpose:

Pregnant women with lupus are at increased risk for complications characterized by insufficient placental vascularization, such as preeclampsia and intrauterine growth restriction. Elevated levels of circulating antiangiogenic factors (sFlt-1 and sEng) and increased rates of increase of these factors through pregnancy predict such complications in healthy women and contribute to disease pathogenesis. Angiogenic imbalance can be triggered by complement activation. We hypothesized that pregnant patients with SLE have altered regulation of anti-angiogenic factors providing a basis for their increased risk for complications.

Methods:

We performed a nested case-control study of SLE patients within the PROMISSE Study (Predictors of pRegnancy Outcome: bioMarkers In antiphospholipid antibody Syndrome and Systemic lupus Erythematosus). Poor pregnancy outcome was defined as: fetal death >12 wks; neonatal death; preeclampsia; preterm delivery <36 wks due to placental insufficiency; or intrauterine growth restriction. We studied 23 SLE patients with poor pregnancy outcomes (SLE/outcome) and 100 SLE patients with uncomplicated pregnancies (SLE/no outcome) matched by age, race/ethnicity to 98 pregnant healthy controls (HC). Subjects were evaluated and blood collected monthly beginning at <12 wks gestation. Mean levels of angiogenic factors were compared between groups at each time point using analysis of variance models. In addition, linear mixed effects models were fit to the data to estimate and compare rates of change in these factors over the entire gestational period.

Results:

The rates of increase in sFlt-1 and sEng through pregnancy were significantly higher in SLE/no outcome patients than HC (p=0.01 and p=0.03, respectively). The rates of rise in sFlt-1 and sEng were also higher in SLE/outcome compared to SLE/no outcome and HC (p < 0.0001). Levels of sFlt-1 and sEng were significantly increased in SLE/outcome compared to HC as early as 20 and 16 wks gestation, respectively, and these differences persisted through 39 wks.

Conclusion:

Angiogenic dysregulation occurs in pregnant SLE patients and may increase their vulnerability to placental insufficiency. Inflammatory mediators associated with SLE, such as complement products and interferon a, create an anti-angiogenic milieu. They may amplify the rates of rise of sFlt-1 and sEng through pregnancy and thereby increase risk for poor placental development and decrease threshold for complications like preeclampsia. We have identified predictors of risk; defining the mediators of angiogenic imbalance will identify targets to treat at-risk patients.

To cite this abstract, please use the following information:
Salmon, Jane E., Kim, Mimi Y., Rana, Sarosh, Guerra, Marta, Lockshin, Michael D., Branch, D. Ware, et al; Angiogenic Factor Imbalance in Pregnant SLE Patients May Explain Increased Risk for Complications [abstract]. Arthritis Rheum 2009;60 Suppl 10 :1747
DOI: 10.1002/art.26821

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