Complement, fetal antigen, and shaking rigors in parturients

Department of Obstetrics and Gynecology, Northwestern University, Evanston, Illinois, United States
Journal of Maternal-Fetal and Neonatal Medicine (Impact Factor: 1.37). 02/2006; 19(1):31-4. DOI: 10.1080/14767050500362206
Source: PubMed


To assess the relationship, if any, between complement, fetal antigen, and shaking rigors during labor and delivery.
We recruited 13 volunteers for serial blood sampling during labor and childbirth.
Complement levels had a small but significant drop (11-15%) immediately following childbirth but had no association with fetal antigen levels or shaking rigors. Fetal antigen levels failed to show any consistent relationship with shaking rigors or the labor and delivery process.
Shaking rigors do not appear to be associated with changes in either complement or fetal antigen levels. Complement levels remain stable during labor but drop immediately following birth.

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    • "C5a up-regulated pro-inflammatory and pro-labor mediators, including pro-inflammatory cytokines (IL-6 and IL-8), cyclooxygenase (COX)-2, PGE2 and PGF2α, matrix metalloproteinase (MMP)-9, and 8-isoprostane in human gestational tissues via the C5a receptor (CD88)-mediated NF-κB activation (Lappas et al., 2012). Abundant research has demonstrated complement activation in an innate immunity of human parturition (Gallery et al., 1981; Benson et al., 2006; Benson, 2007; Soto et al., 2009; Gonzalez et al., 2011; Kato et al., 2012; Lappas et al., 2012), but has yet to investigate whether complement activation is the result of fetal antigen leaking into the maternal circulation. "
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    ABSTRACT: Pro-inflammatory cytokines play an important role during the process of human parturition. The focus of this review was to explore the contribution of biological, biochemical, and genetic changes in the onset of term labor. This article reviews the English-language literature on inflammatory, hormonal, and immunological factors in an effort to identify the molecular basis of human parturition. The majority of the genes and proteins up-regulated in parturition at term are related to four functional categories, mechanical stretch-mediated damage-associated molecular patterns (DAMPs) activation, response to immunity, induction of inflammatory signaling, and progressive uterine myometrial contractility and resultant term birth. Mechanical stretch could promote the entry of amniotic fluid components into the uterine vessel circulation that is the common physiologic mechanism at term prior to labor. The fetal or amniotic fluid-derived DAMPs could activate the immune system. The inflammatory mediators are produced by infiltrating activated leukocytes and by the reproductive tissues themselves such as myometrium, and subsequently lead to uterine contractions. This review supports the sterile inflammation hypothesis that there are at least two phases of human parturition: the initial wave of the entry of amniotic fluid components into uterine vasculatures would be followed by the second big wave of subsequent myometrial contraction.
    Frontiers in Immunology 10/2012; 3:321. DOI:10.3389/fimmu.2012.00321
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    • "A within pairs analysis was performed, and both C3 and C4 demonstrated statistically significant declines, 8% and 5%, respectively. In a second study of twelve healthy American women, serial complement levels were obtained several times during labor and within an hour postpartum [35]. Again, the decreases in complement levels were highly statistically significant with C3 dropping an average of 15% and C4 diminishing by 11%. "
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    ABSTRACT: Amniotic fluid embolism (AFE) is one of the leading causes of maternal mortality and morbidity in developed countries. Current thinking about pathophysiology has shifted away from embolism toward a maternal immune response to the fetus. Two immunologic mechanisms have been studied to date. Anaphylaxis appears to be doubtful while the available evidence supports a role for complement activation. With the mechanism remaining to be elucidated, AFE remains a clinical diagnosis. It is diagnosed based on one or more of four key signs/symptoms: cardiovascular collapse, respiratory distress, coagulopathy, and/or coma/seizures. The only laboratory test that reliably supports the diagnosis is the finding of fetal material in the maternal pulmonary circulation at autopsy. Perhaps the most compelling mystery surrounding AFE is not why one in 20,000 parturients are afflicted, but rather how the vast majority of women can tolerate the foreign antigenic presence of their fetus both within their uterus and circulation?
    Clinical and Developmental Immunology 01/2012; 2012(1740-2522):946576. DOI:10.1155/2012/946576 · 2.93 Impact Factor
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    ABSTRACT: Amniotic fluid embolism, a rare, sudden and often fatal illness of pregnancy may not be a true embolic event resulting from the physical obstruction of the pulmonary vasculature. The high degree of variability in symptoms, the lack of characteristic findings on radiological exam, the absence of a dose-response effect on symptoms, and the occasional occurrence of coagulopathies are not entirely consistent with a physical block to the circulation as the main mechanism of disease. Alternatively, it might be the result of complement activation initiated by fetal antigen leaking into the maternal circulation. This rare immune response may be initiated by a rare pathological antigen, or by common antigens presented uncommonly--in amount, timing, or frequency of entry into the maternal circulation. Some very early evidence in AFE patients supports this hypothesis but is not conclusive. Complement levels remain well within the normal range during uncomplicated parturition. A prior theory that AFE might be a result of maternal anaphylaxis to fetal antigen has much less evidence to support it. The disseminated intravascular coagulation often seen in this and other serious obstetrical illnesses may be a secondary result of complement activation rather than the direct introduction of pro-coagulants into the maternal circulation although the link between the complement and coagulation pathways, if any, remains poorly defined. Through currently available laboratory testing, both the complement hypothesis and the anaphylaxis mechanism are able to be assessed. Direct measurement of serum complement as well as serum tryptase and urinary histamine are readily obtained tests in community hospitals as well as tertiary care hospitals. If the hypothesis proves true, this investigation may be of profound importance to understanding immune tolerance. Rather, than asking why one pregnant woman in 20,000 develops a violent immune reaction to the fetus, a better question is why do not all pregnant women reject the fetus which is a large collection of foreign antigens?
    Medical Hypotheses 02/2007; 68(5):1019-25. DOI:10.1016/j.mehy.2006.09.052 · 1.07 Impact Factor
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