Decreased Levels of Soluble Developmental Endothelial Locus-1 Are Associated with Thrombotic Microangiopathy in Pregnancy

HELLP (Hemolysis, Elevated Liver enzymes and Low Platelets) syndrome is a life-threatening complication of pregnancy, which is often secondary to preeclampsia. To date, there is no biomarker in clinical use for the early stratification of women with preeclampsia who are under increased risk of HELLP syndrome. Herein, we show that the levels of circulating developmental endothelial locus-1 (DEL-1), which is an extracellular immunomodulatory protein, are decreased in patients with HELLP syndrome compared to preeclampsia. DEL-1 levels are also negatively correlated with the circulating levels of kidney injury molecule-1 (KIM-1), which is a biomarker for disorders associated with kidney damage. Receiver-operating characteristic curve analysis for DEL-1 levels and the DEL-1 to KIM-1 ratio demonstrates that these values could be used as a potential biomarker that distinguishes patients with HELLP syndrome and preeclampsia. Finally, we show that placental endothelial cells are a source for DEL-1, and that the expression of this protein in placenta from patients with HELLP syndrome is minimal. Taken together, this study shows that DEL-1 is downregulated in HELLP syndrome both in the circulation and at the affected placental tissue, suggesting a potential role for this protein as a biomarker, which must be further evaluated.

Automated summary

HELLP syndrome, a life-threatening complication of pregnancy, is often related to preeclampsia. However, there is currently no biomarker available for the early identification of pregnant women with preeclampsia who are at an increased risk of developing HELLP syndrome. This study demonstrates that circulating levels of developmental endothelial locus-1 (DEL-1) are decreased in patients with HELLP syndrome compared to those with preeclampsia. DEL-1 levels are also negatively associated with kidney injury molecule-1 (KIM-1) levels. The findings suggest that DEL-1 could potentially be used as a biomarker to distinguish between HELLP syndrome and preeclampsia. Further investigation is needed to confirm these results.