Complement dysregulation underpins pre-eclampsia

By Liam Davenport, medwireNews Reporter

Pre-eclampsia is associated with increased classical pathway activation and altered complement regulation, suggest Dutch results indicating that the extent of complement dysregulation may be related to the severity of pre-eclampsia.

"Altogether, the current data suggest that the complement system plays an essential role in the pathogenesis of pre-eclampsia and may be a novel therapeutic target in the management of pre-eclampsia," suggest the researchers, led by Aletta Buurma, from Leiden University Medical Center.

In an accompanying editorial in Hypertension, Jeffery Gilbert, from the University of Oregon, in Eugene, USA, notes: "The question specific to both local and systemic complement activation remains: is it excessive activation, inadequate control, or both?

"Studies in our laboratories and others are working toward answering these questions with hopes of identifying significant new therapeutic targets [and] minimize the necessity for preterm delivery of the fetus."

Placentas from 28 women with pre-eclampsia and 44 healthy control women who delivered between 2002 and 2011 were studied. Alongside increased blood pressure and proteinuria, pre-eclamptic women had a lower mean gestational age at delivery, infant birthweight, and placenta weight.

C4d, a component of both the classical and mannose-binding lectin pathways, was detected in 50% of placentas from pre-eclamptic women, compared with just 3% of those from healthy controls.

C4d was observed at the syncytiotrophoblast in a focal or diffuse staining pattern. There was a trend for association between immune deposits at the syncytiotrophoblast and C4d, with immune deposits in 23% of placentas with no or minimal C4d, deposits in 44% of placentas with focal C4d, and deposits in 60% of placentas with diffuse C4d.

Although C4d staining was not associated with pre-eclampsia onset, the height of blood pressure, or the amount of urinary protein, there was a significant association between diffuse staining and lower gestational age at delivery and lower infant birthweight among pre-eclamptic women.

There were no differences between cases and controls in terms of C1q, mannose-binding lectin, and properdin staining. However, messenger RNA expression of the regulatory proteins CD55 and CD59 was significantly increased in pre-eclampsia.

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