Functional analysis of the mannose-binding lectin complement pathway in normal pregnancy and preeclampsia

Abstract

Preeclampsia is a severe complication of pregnancy characterized by hypertension and proteinuria developing after midgestation. Previous studies have shown increased complement activation in normal and preeclamptic pregnancies. We aimed to investigate the role of the mannose-binding lectin pathway in the initiation of pathological complement activation observed in patients with preeclampsia. The study included 60 preeclamptic patients, 60 healthy pregnant women and 56 healthy non-pregnant women. Functional activity of the complex of mannose-binding lectin and mannose-binding lectin-associated serine protease 2 (MBL-MASP2 complex) was determined by ELISA. Circulating levels of complement components and C-reactive protein (CRP) were also measured. MBL-MASP2 activity was significantly higher in healthy pregnant than non-pregnant women. However, increased activity of the MBL-MASP2 complex in preeclamptic patients was not observed, compared to healthy pregnant women. MBL-MASP2 activity showed no relationship with either the levels of complement parameters, or with the clinical data and level of CRP in patients with preeclampsia. In conclusion, the complement system is activated with increased terminal complex formation in the third trimester of normal human pregnancy, and is further activated in preeclampsia as shown by the elevated amounts of activation markers. The activity of MBL-MASP2 is also increased in normal pregnancy, to the same level seen in preeclampsia. In our study, no relationship between MBL-MASP2 activity and extent of complement activation was observed in preeclampsia. We tentatively conclude, albeit without an evaluation of local placental concentrations, that the mannose-binding lectin pathway may play only a minor role in pathological complement activation during preeclampsia.