Geburtshilfe Frauenheilkd 2006; 66 - PO_G_04_29
DOI: 10.1055/s-2006-952888

Relation between AT1 receptor agonistic autoantibodies and soluble fms-like tyrosine kinase 1 in the pathogenesis of preeclampsia

H Stepan 1, R Faber 1, N Wessel 2, G Wallukat 3, T Walther 4
  • 1Universitätsfrauenklinik Leipzig, Leipzig
  • 2Institut für Physik, Universität Potsdam, Potsdam
  • 3Max-Delbrück-Centrum für Molekulare Medizin Berlin-Buch, Berlin
  • 4Department of Pharmacology, Erasmus Medical Center, Rotterdam, Niederlande

Aims: Soluble fms-like tyrosine kinase 1 (sFlt1) has shown to be elevated in pregnant women with preeclampsia (PE) or IUGR. Recent studies have also demonstrated an autoantibody against the angiotensin AT1 receptor (AT1-AA) in these pregnancy complications. Both factors are discussed to be key players in the etiology of the disease. However, there is no information, whether these two circulating factors correlate and if their possible synergy may determine the severity of pathology.

Methods: AT1-AA was determined by a functional bioassay and sFlt1 by an ELISA in second trimester pregnancies with normal (n=15) or abnormal uterine perfusion (n=36). Additionally, third trimester pregnancies with manifest preeclampsia (n=18) or IUGR (n=9) were investigated.

Results: In pregnancies with normal perfusion, AT1-AA was not detectable. While AT1-AA was detected in 60% of the pregnancies with abnormal uterine perfusion without later pathology, sFlt1 did not differ significantly compared to pregnancies with normal uterine perfusion. However, while women with abnormal perfusion and later pregnancy pathology did not differ significantly in AT1-AA prevalence (73%) compared to those with normal outcome (60%), sFlt1 was significantly increased (3481±1212 vs. 416.1±50.8 pg/ml, P<0.001). In these groups, the two factors did not correlate (p=0.15). Third trimester patients with manifest preeclampsia or IUGR were characterized by high sFlt1 levels (PE: 9504±1441 pg/ml, IUGR: 7195±1247 pg/ml) and the AT1-AA positive rate was 89% in both groups. Again, AT1-AA activity did not correlate with sFlt1 concentrations (p=0.85).

Conclusion: We conclude that the AT1-AA bioactivity and the sFlt1 concentrations do not correlate, are not mutually dependent, and therefore seem to be involved in distinct pathogenetic mechanisms. Both factors in combination may not be causative for the early impaired trophoblast invasion and pathological uterine perfusion.