Complement in Pregnancy: A Delicate Balance

Denny, Kerina J.; Woodruff, Trent M.; Taylor, Stephen M.; Callaway, Leonie K.

doi:10.1111/aji.12000

Cited by 74 publications

(95 citation statements)

References 83 publications

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“…C3a is a cleavage product that functions as an anaphylatoxin, which recruits and activates inflammatory cells, amplifies local inflammation, and effects vascular permeability and smooth muscle contractility (Sjoberg et al, 2009; Walport, 2001). C3b opsonizes pathogens and/or non-self cells for destruction by phagocytic cells, and also initiates the activation of downstream complement proteins that form the membrane attack complex (C5-C9), leading to pathogen cell lysis and death (Denny et al, 2013; Lynch et al, 2011; Markiewski & Lambris, 2007). Factors B, D, and properdin lead to the activation of C3 via the alternative pathway; Bb a derivative of Factor B, is an activation product that assists in the additional cleavage of component C3 (Lynch et al, 2008).…”

Section: The Microbiome As a Mechanism For Preterm Birthmentioning

confidence: 99%

The Microbiome and Complement Activation: A Mechanistic Model for Preterm Birth

Dunn

Dunlop

Hogue

et al. 2017

Biological Research For Nursing

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Preterm Birth (PTB, < 37 completed weeks' gestation) is one of the leading obstetrical problems in the United States affecting approximately 1 of every 9 births. Even more concerning are the persistent racial disparities in PTB with particularly high rates in African Americans. There are several recognized pathophysiologic pathways to PTB, including infection and/or exaggerated systemic or local inflammation. Intrauterine infection is a causal factor linked to PTB, thought to result most commonly from inflammatory processes triggered by microbial invasion of bacteria ascending from the vaginal microbiome. Trials to treat various infections have shown limited efficacy in reducing PTB risk, suggesting that other complex mechanisms, including those associated with inflammation, may be involved in the relationship between microbes, infection, and PTB. A key mediator of the inflammatory response, and recently shown to be associated with PTB, is the complement system, an innate defense mechanism involved in both normal physiologic processes that occur during pregnancy implantation, as well as processes that promote the elimination of pathogenic microbes. The purpose of this paper is to present a mechanistic model of inflammation-associated PTB, which hypothesizes a relationship between the microbiome and dysregulation of the complement system. Exploring the relationships between the microbial environment and complement biomarkers may elucidate a potentially modifiable biological pathway to preterm birth.

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Section: The Microbiome As a Mechanism For Preterm Birthmentioning

confidence: 99%

The Microbiome and Complement Activation: A Mechanistic Model for Preterm Birth

Dunn

Dunlop

Hogue

et al. 2017

Biological Research For Nursing

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“…These mediate the clearance of pathogens, apoptotic cells, and immune complexes by forming a membrane attack complex (MAC), which leads to cell lysis [54, 55]. The complement system can be activated in three pathways: the classic pathway is triggered by antigen-antibody complexes; the alternative pathway is spontaneously and continuously activated; the lectin pathway is triggered by the binding of mannan-binding lectin to mannose residues on the surface of microorganisms [54, 55]. Irrespectively of the mechanism of activation, all the pathways converge to generate C3 convertases, which transform C3 into its active components, C3a and C3b.…”

Section: Maternofetal Immunologymentioning

confidence: 99%

Relationship between Maternal Immunological Response during Pregnancy and Onset of Preeclampsia

Martínez-Varea

Pellicer

Perales‐Marín

et al. 2014

Journal of Immunology Research

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Maternofetal immune tolerance is essential to maintain pregnancy. The maternal immunological tolerance to the semiallogeneic fetus becomes greater in egg donation pregnancies with unrelated donors as the complete fetal genome is allogeneic to the mother. Instead of being rejected, the allogeneic fetus is tolerated by the pregnant woman in egg donation pregnancies. It has been reported that maternal morbidity during egg donation pregnancies is higher as compared with spontaneous or in vitro fertilization pregnancies. Particularly, egg donation pregnancies are associated with a higher incidence of pregnancy-induced hypertension and placental pathology. Preeclampsia, a pregnancy-specific disease characterized by the development of both hypertension and proteinuria, remains the leading cause of maternal and perinatal mortality and morbidity. The aim of this review is to characterize and relate the maternofetal immunological tolerance phenomenon during pregnancies with a semiallogenic fetus, which are the spontaneously conceived pregnancies and in vitro fertilization pregnancies, and those with an allogeneic fetus or egg donation pregnancies. Maternofetal immune tolerance in uncomplicated pregnancies and pathological pregnancies, such as those with preeclampsia, has also been assessed. Moreover, whether an inadequate maternal immunological response to the allogenic fetus could lead to a higher prevalence of preeclampsia in egg donation pregnancies has been addressed.

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“…The adaptive and the innate arms of the immune system are both involved in this process and develop strategies to establish a protective environment in maternal decidua to prevent fetal demise (1). C is a humoral component of innate immunity, which fulfills protective functions providing a critical defense barrier against infectious agents potentially harmful to the fetus (2,3). More recent findings have also disclosed the important role of C in placental development in normal pregnancy by promoting tissue remodeling and vascular changes (4).…”

mentioning

confidence: 99%

Critical Role and Therapeutic Control of the Lectin Pathway of Complement Activation in an Abortion-Prone Mouse Mating

Petitbarat

Durigutto

Macor

et al. 2015

The Journal of Immunology

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The abortion-prone mating combination CBA/J × DBA/2 has been recognized as a model of preeclampsia, and complement activation has been implicated in the high rate of pregnancy loss observed in CBA/J mice. We have analyzed the implantation sites collected from DBA/2-mated CBA/J mice for the deposition of the complement recognition molecules using CBA/J mated with BALB/c mice as a control group. MBL-A was observed in the implantation sites of CBA/J × DBA/2 combination in the absence of MBL-C and was undetectable in BALB/c-mated CBA/J mice. Conversely, C1q was present in both mating combinations. Searching for other complement components localized at the implantation sites of CBA/J × DBA/2, we found C4 and C3, but we failed to reveal C1r. These data suggest that complement is activated through the lectin pathway and proceeds to completion of the activation sequence as revealed by C9 deposition. MBL-A was detected as early as 3.5 d of pregnancy, and MBL-A deficiency prevented pregnancy loss in the abortion-prone mating combination. The contribution of the terminal complex to miscarriage was supported by the finding that pregnancy failure was largely inhibited by the administration of neutralizing Ab to C5. Treatment of DBA/2-mated CBA/J mice with Polyman2 that binds to MBL-A with high affinity proved to be highly effective in controlling the activation of the lectin pathway and in preventing fetal loss.

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Complement in Pregnancy: A Delicate Balance

Cited by 74 publications

References 83 publications

The Microbiome and Complement Activation: A Mechanistic Model for Preterm Birth

The Microbiome and Complement Activation: A Mechanistic Model for Preterm Birth

Relationship between Maternal Immunological Response during Pregnancy and Onset of Preeclampsia

Critical Role and Therapeutic Control of the Lectin Pathway of Complement Activation in an Abortion-Prone Mouse Mating

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