Maternal and Fetal Alternative Complement Pathway Activation in Early Severe Preeclampsia

Abstract

Problem We sought to determine whether alternative complement activation fragment Bb (Bb) levels are elevated in the maternal, fetal, and placental blood in cases of severe preeclampsia (PE) compared with normotensive controls. Method of study This was a cross-sectional study of women admitted at ≥24 weeks gestation with or without severe PE. Maternal plasma was collected at the time of enrollment. Umbilical venous cord and intervillous space blood were collected at delivery. Plasma Bb levels were assessed using ELISA. Bb levels were compared between cases and controls. Results Median Bb levels were higher in the maternal plasma of severe PE subjects (n = 24) than in controls (n = 20), 1.45 ± 1.03 versus 0.65 ± 0.23 μg/mL, P < 0.001. In umbilical venous plasma, Bb levels were higher in severe PE subjects (n = 15) compared with controls (n = 15), 2.48 ± 1.40 versus 1.01 ± 0.57 μg/mL, P = 0.01. Conclusion Activation fragment Bb is increased in the maternal and umbilical venous blood of cases of severe PE when compared with normotensive controls. These data provide support for alternative complement pathway involvement in the pathogenesis of severe PE and demonstrate that alternative complement activation occurs not only in the maternal but also in the fetal compartment.

Preeclampsia is Characterized by Fetal NK Cell Activation and a Reduction in Regulatory T Cells

“…Increased inflammation and activation of the Alternative Complement Pathway in cord blood of babies born to preeclamptic mothers have been observed suggesting that maternal preeclampsia does indeed have consequences for the fetal immune system 22, 23. Bujold et al 20.…”

Innate Immune System at the Maternal–Fetal Interface: Mechanisms of Disease and Targets of Therapy in Pregnancy Syndromes

“…While not all related studies have been conclusive, both the classical and the alternative CS pathway have been recognized in the pathogenesis of PE. 10,37,38 Bb fragments may represent a sign of the exaggerated alternative CS pathway activation occurring in the early severe PE. 38 Clinical studies reported that CS is activated with increased terminal complex (C5b9) formation in the third trimester of normal human pregnancy, and further in PE.…”

Atypical hemolytic-uremic syndrome in obstetric practice: The first Russian experience of diagnosis and treatment

“…В пользу этого свидетельствует обнаруженное до 20 нед гестации в крови беременных с развившейся впоследствии преэклампсией высокое содержание одного из важных факторов, форми-рующих С3-конвертазу АПК -фрагмента комплемента Bb [14]. Позже был продемонстрирован повышенный уровень Bb в плазме крови пациенток с рано развившейся (до 34 нед беременности) тяжелой преэклампсией и в ве-нозной пуповинной крови детей, рожденных этими мате-рями, по сравнению с таковыми у женщин с неосложнен-ным течением беременности, что подтвердило важную роль системной активации АПК в развитии преэкламп-сии [16]. Кроме того, оказалось, что комплементы актива-ции комплемента, особенно фрагмент С5а, стимулируют продукцию моноцитами растворимых рецепторов к фак-тору роста эндотелия сосудов (VEGF) -sVEGFR-1 или sFlt1, которые блокируют плацентарные ангиогенные факторы VEGF и PlGF.…”