Pregnancy in Autoimmune Disease

Meghan Clowse, M. D.

Abstract 553:  Soluble FMS-Like Tyrosine Kinase is a Significant Predictor of Preeclampsia in SLE Pregnancy

Authors: Umair M. Qazi1, Chun Lam2, Ananth Karumanchi2, Michelle Petri1. 1Johns Hopkins University, Sch of Med., Baltimore, MD; 2Harvard University, Boston, MA

In this case-control study of lupus pregnancies, the authors identify elevated sFlt-1 (soluble FMS-like tyrosine kinase-1) as a marker of preeclampsia in SLE pregnancies.  Fifty-two pregnancies in women with lupus were studied, 18 (35%) with preeclampsia.  Preeclampsia was defined at either new hypertension & proteinuria, or a sudden increase in blood pressure & proteinuria in the latter half of pregnancy. 

Among patients with preeclampsia, the sFLT level was 1768 +/- 196, significantly higher than in women without preeclampsia.  Blood levels were drawn between gestational weeks 22-32, however it is unclear whether preeclampsia was already present when the labs were taken. 

The authors also report on PlGF (placental growth factor), postulated to be a good marker of preeclampsia in non-SLE pregnancies.  This study did not find a difference between the PlGF levels of women with and without preeclampsia.

Editorial:  Biomarkers for preeclampsia are sorely needed to improve the pregnancy outcomes of all women, but especially women with lupus who are much greater risk for this complication. 

sFlt-1 is an anti-angiogenic protein that is increased in the placenta and serum of women with preeclampsia.  By binding to placental growth factor (PlGF) and vascular endothelial growth factor (VEGF), it prevents their interaction with endothelial cells.  This impairs the vasodilation needed in the placenta to feed the fetus, and results in maternal hypertension.  An elevation in sFlt-1, a drop in PlGF, and an elevation in the ratio of sFlt-1:PlGF has been associated with preeclampsia in non-SLE pregnancies.

The blood levels of SFlt-1 and PlGF vary dramatically over the course of pregnancy; sFLT-1 has an average level at 32 weeks (1,130 pg/ml) that is almost 3 times higher than at 28 weeks (413 pg/ml).  For PlGF, the level at 28 weeks (513 pg/ml) is higher than at 32 weeks (354 pg/ml) As the blood used in this study came from a wide-range of gestational ages, it is difficult to know how to interpret this data. 

This study suggests that evaluation of angiogenic factors that promote preeclampsia is a worthwhile avenue of research in SLE pregnancies.  These tests are not yet ready for routine clinical use, however.  It remains to be determined whether these factors can be used to distinguish a lupus nephritis flare from preeclampsia.  This is one of the largest clinical challenges in the treatment of lupus pregnancy, and a reliable tool to do so would be a major breakthrough.

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