title: OS004. A link between the complement system and angiogenic imbalance inpreeclampsia: ficolin-2 deficiency.
abstract: BACKGROUND
  An excessive maternal systemic inflammatory response to pregnancy, as well as an imbalance between circulating angiogenic factors and their antagonists plays a central role in the pathogenesis of preeclampsia. The complement system, as part of innate immunity, is fundamental to the host's immune defense against microbial pathogens, apoptotic and necrotic cells. Both of its excessive activation and deficiencies can lead to various disorders.
  
  
  OBJECTIVE
  The aim of this study was to determine circulating levels of components of the complement system and their relationship to those of angiogenic factors in normal pregnancy and preeclampsia.
  
  
  METHODS
  Sixty preeclamptic patients, 60 healthy pregnant women and 59 healthy non-pregnant women were involved in this case-control study. Circulating levels of C1rC1sC1-inh, C3bBbP, C4d, C3a, SC5b9, ficolin-2, ficolin-3, soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF), as well as activity of the complex of mannose-binding lectin and mannose-binding lectin-associated serine protease 2 (MBL-MASP2 complex) were measured. For statistical analyses, non-parametric methods were applied.
  
  
  RESULTS
  Circulating levels of C3bBbP, C4d, C3a, SC5b9, sFlt-1, PlGF, as well as MBL-MASP2 activity were significantly higher, while ficolin-2 concentrations were significantly lower in healthy pregnant than in healthy non-pregnant women. Furthermore, preeclamptic patients had significantly higher C1rC1sC1-inh, C3bBbP, C4d, C3a, SC5b9 and sFlt-1 levels and significantly lower ficolin-2, ficolin-3 and PlGF concentrations than healthy pregnant women. In the groups of healthy pregnant women and preeclamptic patients, plasma ficolin-2 levels showed a significant positive correlation with serum PlGF concentrations and a significant inverse correlation with serum levels of sFlt-1. There was no other relationship between complement components and angiogenic factors in either study group.
  
  
  CONCLUSIONS
  Elevated levels of activation products in the systemic circulation indicate complement activation with increased terminal complex formation in preeclampsia, which seems to be independent from alterations in circulating angiogenic factors. Nevertheless, low ficolin-2 concentrations might contribute to the angiogenic imbalance in preeclampsia by impaired removal of the sFlt-1-containing trophoblast-derived material released into the maternal circulation by the hypoxic and oxidatively stressed preeclamptic placenta.
authors.affiliation: First Department of Obstetrics and Gynecology.
authors.forename: A
authors.initials: A
authors.lastname: Molvarec
authors.affiliation: First Department of Obstetrics and Gynecology.
authors.forename: A
authors.initials: A
authors.lastname: Halmos
authors.affiliation: First Department of Obstetrics and Gynecology.
authors.forename: J
authors.initials: J
authors.lastname: Szijártó
authors.affiliation: Third Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: D
authors.initials: D
authors.lastname: Csuka
authors.affiliation: Third Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: G
authors.initials: G
authors.lastname: Füst
authors.affiliation: Third Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Z
authors.initials: Z
authors.lastname: Prohászka
authors.affiliation: First Department of Obstetrics and Gynecology.
authors.forename: J
authors.initials: J
authors.lastname: Rigó