Complement factor B activation in patients with preeclampsia

Abstract

Preeclampsia is a leading cause of maternal and fetal morbidity and mortality. Bb, the active fragment of complement factor B (fB), has been reported to be a predictor of preeclampsia. However, conflicting results have been found by some investigators. We hypothesized that the disagreement in findings may be due to the racial/ethnic differences among various study groups, and that fB activation is significant in women of an ethnic minority with preeclampsia. We investigated the maternal and fetal levels of Bb (the activated fB fragment) in pregnant women of an ethnic minority with or without preeclampsia. We enrolled 291 pregnant women (96% of an ethnic minority, including 78% African–American). Thirteen percent of these were diagnosed with preeclampsia. Maternal venous blood was collected from all participants together with fetal umbilical cord blood samples from 154 deliveries in the 291 women. The results were analyzed using the Mann–Whitney U test and multivariate analyses. Maternal Bb levels were significantly higher in the preeclamptic group than in the nonpreeclamptic group. Levels of Bb in fetal cord blood were similar in both groups. Subgroup analyses of African–American patients’ results confirmed the study hypothesis that there would be a significant increase in Bb in the maternal blood of the preeclamptic group and no increase in Bb in the fetal cord blood of this group. These results suggest that a maternal immune response through complement fB might play a role in the development of preeclampsia, particularly in African–American patients.

Serum Adipsin Levels throughout Normal Pregnancy and Preeclampsia

“…Previous studies have determined the complement-activation of fragment Bb in preeclamptic and healthy pregnant women in early and late stages of pregnancy. A significant increase was observed in the levels of factor Bb in the group of women with preeclampsia than in controls 58 59 . Thus, the rise in Bb levels correlates with increased adipsin levels in the present study, where a statistically significant increment during the late pregnancy of preeclamptic women is observed.…”

Normal range of complement components during pregnancy: A prospective study

“…C1q is the core molecule in the classical pathway of complement activation and is widely distributed in the human decidual stroma. [17][18][19][20][21][22][23] Therefore, establishing a normal range of complement components during pregnancy is important for clinical evaluation and research. [8][9][10] Complement factor B (CFB) can bind to C3b to form C3 convertase, promoting activation of the complement system via the alternative pathway, and this process can be inhibited by complement factor H (CFH), an inhibitor of the alternative pathway.…”

“…11,12 In general, moderate activation of the complement system is crucial for maintaining pregnancy, and any deviation from normal activation and regulation of the complement system may result in adverse pregnancy outcomes, such as recurrent spontaneous abortion, 13 preterm birth, [14][15][16] and preeclampsia. [17][18][19][20][21][22][23] Therefore, establishing a normal range of complement components during pregnancy is important for clinical evaluation and research. In addition, changes in circulating complement components may provide accessible biomarkers for predicting adverse pregnancy outcomes if "normal" pregnancy components are understood.…”

Expression of the complement system's activation factors in plasma of patients with early/late‐onset severe pre‐eclampsia

“…If the complement system is overactivated, however, the activating complement component C3a can activate a maternal systemic inflammatory response, leading to the corresponding manifestations of pre‐eclampsia . In recent years, many studies have investigated the complement activation situation in the maternal circulation of pre‐eclampsia patients, finding a higher expression of complement activation factors in the maternal circulation compared to normal pregnant women, although some studies did not find this phenomenon . Therefore, there is still a debate about the complement activation situation in the maternal circulation of pre‐eclampsia patients.…”