title: Interferon-α and angiogenic dysregulation in pregnant lupus patients who develop preeclampsia.
abstract: 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 responses to soluble Flt-1. In a model of spiral artery transformation, only the combination of IFNα and soluble Flt-1 disrupted the ability of trophoblast cells to remodel endothelial tube structures.
  
  
  CONCLUSIONS
  Our findings identify a new mechanism by which IFNα induces an antiangiogenic milieu and increases the sensitivity of endothelial cells to soluble Flt-1, and suggest that elevated IFNα levels may contribute to the pathogenesis of preeclampsia in some pregnant patients with SLE.
authors.affiliation: Hospital for Special Surgery and Weill Cornell Medical College, New York, New York.
authors.forename: Danieli
authors.initials: D
authors.lastname: Andrade
authors.forename: Mimi
authors.initials: M
authors.lastname: Kim
authors.forename: Luz P
authors.initials: LP
authors.lastname: Blanco
authors.forename: S Ananth
authors.initials: SA
authors.lastname: Karumanchi
authors.forename: Gloria C
authors.initials: GC
authors.lastname: Koo
authors.forename: Patricia
authors.initials: P
authors.lastname: Redecha
authors.forename: Kyriakos
authors.initials: K
authors.lastname: Kirou
authors.forename: Angela M
authors.initials: AM
authors.lastname: Alvarez
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Mulla
authors.forename: Mary K
authors.initials: MK
authors.lastname: Crow
authors.forename: Vikki M
authors.initials: VM
authors.lastname: Abrahams
authors.forename: Mariana J
authors.initials: MJ
authors.lastname: Kaplan
authors.forename: Jane E
authors.initials: JE
authors.lastname: Salmon
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000097:blood*; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000150:complications; D000072483:Placenta Growth Factor; D011225:Pre-Eclampsia / Q000097:blood*; D011247:Pregnancy; D011256:Pregnancy Outcome; D011257:Pregnancy Proteins / Q000097:blood*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood*
chemical_list: D016898:Interferon-alpha; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D000072483:Placenta Growth Factor; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1