Interferon‐α and Angiogenic Dysregulation in Pregnant Lupus Patients Who Develop Preeclampsia

作者：DANIELI CASTRO OLIVEIRA DE ANDRADE, Mimi Kim, Luz P. Blanco, S. Ananth Karumanchi, Gloria C. Koo, Patricia B. Redecha, Kyriakos A. Kirou, Ángela M. Álvarez, Melissa J. Mulla, Mary K. Crow, Vikki M. Abrahams, Mariana J. Kaplan, Jane E. Salmon · 发表于：Arthritis & Rheumatology · 年份：2015 · DOI：10.1002/art.39029 · 被引用次数：85 · 研究领域：Systemic Lupus Erythematosus Research、Pregnancy and preeclampsia studies、Reproductive System and Pregnancy

OBJECTIVE: To investigate whether an elevated interferon-α (IFNα) level early in pregnancy is associated with poor pregnancy outcomes and to examine the relationship of an elevated IFNα level to angiogenic imbalance. METHODS: Women were enrolled in a longitudinal case-control study of pregnant patients with lupus. Serum samples obtained monthly throughout pregnancy were assayed for IFNα and for the antiangiogenic factor soluble Flt-1 and the proangiogenic factor placenta growth factor (PlGF). Each of 28 patients with systemic lupus erythematosus (SLE) with a poor pregnancy outcome was matched to an SLE patient with an uncomplicated pregnancy and to a pregnant healthy control. The effects of IFNα and/or soluble Flt-1 on human endothelial cells and endothelial cell-trophoblast interactions were assessed. RESULTS: Compared to SLE patients with uncomplicated pregnancies, patients with preeclampsia had increased IFNα levels before clinical symptoms. Patients without autoimmune disease who developed preeclampsia did not have increased IFNα levels. In SLE patients with low IFNα levels, marked angiogenic imbalance (higher soluble Flt-1, lower PlGF, and higher soluble Flt-1:PlGF ratios) preceded maternal manifestations of preeclampsia, whereas in SLE patients with high IFNα levels, preeclampsia occurred without evidence of systemic angiogenic imbalance. Treatment of human endothelial cells with soluble Flt-1 induced expression of sFLT1 messenger RNA, and IFNα dramatically amplified re...