Activation of the complement system in normal pregnancy and preeclampsia

Derzsy, Zoltán; Prohászka, Zoltán; Rigó, János; Füst, George; Molvarec, Attila

doi:10.1016/j.molimm.2010.01.021

Cited by 234 publications

(251 citation statements)

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“…Our data indicated that activation of the classical/lectin and alternative pathways that lead to the activation of the terminal pathway was present in TTP. It is known Thrombosis Research 133 (2014) [616][617][618][619][620][621] that activation of the complement system and of neutrophil granulocytes is characteristic for most infections and also in pregnancy, especially if complicated with preeclapmsia and/or fetal growth restriction [12,13]. Therefore, we hypothesized that neutrophil activation may associate with acute, ADAMTS13-deficient TTP and potentially contribute to the development of clinically active thrombotic microangiopathy.…”

Section: Introductionmentioning

confidence: 99%

Elevated plasma neutrophil elastase concentration is associated with disease activity in patients with thrombotic thrombocytopenic purpura

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Sinkovits

Farkas

et al. 2014

Thrombosis Research

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Keywords:Polymorphonuclear leukocyte neutrophil granulocyte elastase thrombotic thrombocytopenic purpura disease activity complement activation Introduction: Genetic and autoimmune risk factors contribute to the development of thrombotic thrombocytopenic purpura (TTP) but triggers are needed to bring about acute disease. The aim of the study was to investigate the association of neutrophil activation with acute TTP, to assess whether neutrophil activation changes during plasma exchange therapy and to show if complement-and neutrophil activation are parallel, characteristic processes in acute TTP. Materials and Methods: Altogether 49 EDTA-plasma samples of 21 TTP patients with acute disease and 17 in remission were investigated along with 20 healthy controls. A stable complex of PMNE-proteinase-inhibitor was measured by ELISA (Calbiochem, Merck-Millipore, Darmstadt, Germany). Results: Acute disease was associated with significantly increased PMNE levels, the group medians were similarly low in TTP patients in remission and in healthy controls. Increased PMNE levels were characteristic for hematologically active and ADAMTS13 deficient form of TTP. PMNE concentration inversely correlated to disease activity markers platelet count (r = − 0.349, p = 0.032) and hemoglobin levels (p = − 0.382 p = 0.018). Achievement of remission was associated with significant reduction of plasma PMNE levels (p = 0.031, Wilcoxon test). There was positive correlation between PMNE levels and complement activation markers C3a and Bb. Conclusions: We report increased PMNE levels in acute TTP and showed its association to activity markers of acute TTP and complement activation. Effective treatment of an acute TTP episode resulted in marked decrease in PMNE levels. Our data support and extend previous observations that neutrophil extracellular traps may be released in acute TTP and potentially contribute to the pathophysiology of this disease.

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Section: Introductionmentioning

confidence: 99%

Elevated plasma neutrophil elastase concentration is associated with disease activity in patients with thrombotic thrombocytopenic purpura

Mikes

Sinkovits

Farkas

et al. 2014

Thrombosis Research

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“…Thirty‐two studies in total reported on C‐reactive protein levels,21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52 of which 17 were applicable for meta‐analysis 21, 22, 23, 29, 30, 31, 32, 33, 34, 37, 38, 39, 41, 42, 47, 49, 50. A significantly higher C‐reactive protein was found in women with pre‐eclampsia than in non‐hypertensive controls ( Figure 2), and this correlation was stronger in severe than in mild pre‐eclampsia ( Figure 3).…”

Section: Resultsmentioning

confidence: 99%

Shared biomarkers between female diastolic heart failure and pre‐eclampsia: a systematic review and meta‐analysis

et al. 2017

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Evidence accumulates for associations between hypertensive pregnancy disorders and increased cardiovascular risk later. The main goal of this study was to explore shared biomarkers representing common pathogenic pathways between heart failure with preserved ejection fraction (HFpEF) and pre‐eclampsia where these biomarkers might be potentially eligible for cardiovascular risk stratification in women after hypertensive pregnancy disorders. We sought for blood markers in women with diastolic dysfunction in a first literature search, and through a second search, we investigated whether these same biochemical markers were present in pre‐eclampsia.This systematic review and meta‐analysis presents two subsequent systematic searches in PubMed and EMBASE. Search I yielded 3014 studies on biomarkers discriminating women with HFpEF from female controls, of which 13 studies on 11 biochemical markers were included. Cases had HFpEF, and controls had no heart failure. The second search was for studies discriminating women with pre‐eclampsia from women with non‐hypertensive pregnancies with at least one of the biomarkers found in Search I. Search II yielded 1869 studies, of which 51 studies on seven biomarkers were included in meta‐analyses and 79 studies on 12 biomarkers in systematic review.Eleven biological markers differentiated women with diastolic dysfunction from controls, of which the following 10 markers differentiated women with pre‐eclampsia from controls as well: C‐reactive protein, HDL, insulin, fatty acid‐binding protein 4, brain natriuretic peptide, N terminal pro brain natriuretic peptide, adrenomedullin, mid‐region pro adrenomedullin, cardiac troponin I, and cancer antigen 125.Our study supports the hypothesis that HFpEF in women shares a common pathogenic background with pre‐eclampsia. The biomarkers representing inflammatory state, disturbances in myocardial function/structure, and unfavourable lipid metabolism may possibly be eligible for future prognostic tools.

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“…8,9 The complement system, an important component of innate immunity, plays a pivotal role in recruiting inflammatory and immunocompetent cells contributing to various immune and inflammatory diseases. Several complications of pregnancy, including spontaneous pregnancy losses, 10,11 pre-eclampsia, 12,13 and pre-term labor 14 -18 have been associated with a maternal complement activation. Importantly, increased activation of complement components in maternal blood and the amniotic fluid has been reported in patients with preterm delivery.…”

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Complement Activation Triggers Metalloproteinases Release Inducing Cervical Remodeling and Preterm Birth in Mice

González

Franzke

Yang

et al. 2011

The American Journal of Pathology

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Inflammation is frequently linked to preterm delivery (PTD). Here, we tested the hypothesis that complement activation plays a role in cervical remodeling and PTD. We studied two mouse models of inflammation-induced PTD. The first model was induced by vaginal administration of lipopolysaccharide (LPS) and the second one by administration of progesterone antagonist RU486. Increased cervical C3 deposition and macrophages infiltration and increased serum C3adesArg and C5adesArg levels were observed in both models when compared to gestational age matched controls. A significant increase in collagen degradation, matrix metalloproteinase 9 (MMP-9) activity and tissue distensibility was observed in the cervix in both models. Mice deficient in complement receptor C5a did not show increased MMP-9 activity and cervical remodeling and did not deliver preterm in response to LPS or RU486, suggesting a role for C5aR in the cervical changes that precede PTD. In vitro studies show that macrophages release MMP-9 in response to C5a. Progesterone diminished the amount of C5aR on the macrophages surface, inhibited the release of MMP-9 and prevented PTD. In addition, macrophages depletion also prevented cervical remodeling and PTD in LPS-treated mice. Our studies show that C5a-C5aR interaction is required for MMP-9 release from macrophages, and the cervical remodeling that leads to PTD. Complement inhibition and supplementation with progesterone may be good therapeutic options to prevent this serious pregnancy complication. Premature birth/delivery (PTD) is one of the most significant causes of perinatal mortality and morbidity in developed countries. Preterm infants suffer morbidities including respiratory distress, intraventricular hemorrhage, and cerebral palsy, among other serious diseases.1 These outcomes can have a life-long impact and more than $25 billion is spent each year to take care of these infants. Investigations to define the causes of PTD remain a challenge in the obstetrical field. Preterm labor is a multistage biochemical and biophysical process, during which changes in the myometrium and the cervix occur.The uterine cervix is a complex organ that undergoes extensive changes through gestation and parturition. These changes are a common first step in preterm parturition.2 As a gatekeeper for pregnancy, the cervix is a structural barrier that keeps the fetus inside the uterus until the end of gestation. Collagens, elastin, proteoglycans, and hyaluronate are responsible for the full tensile strength of the cervix.2 Ripening of the cervix is an important biological and clinical event required for a normal parturition. The process is gradual during pregnancy, with a fast final remodeling of the cervix before parturition. Increased collagen degradation and synthesis, and high activity of collagenases have been observed in the human cervix during final ripening.

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Activation of the complement system in normal pregnancy and preeclampsia

Cited by 234 publications

References 45 publications

Elevated plasma neutrophil elastase concentration is associated with disease activity in patients with thrombotic thrombocytopenic purpura

Elevated plasma neutrophil elastase concentration is associated with disease activity in patients with thrombotic thrombocytopenic purpura

Shared biomarkers between female diastolic heart failure and pre‐eclampsia: a systematic review and meta‐analysis

Complement Activation Triggers Metalloproteinases Release Inducing Cervical Remodeling and Preterm Birth in Mice

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