Serum Amyloid A Protein and C-Reactive Protein in Normal Pregnancy and Preeclampsia

Kristensen, Karl; Wide‐Swensson, Dag; Lindström, Veronica; Schmidt, C. N. G.; Grubb, Anders; Strevens, Helena

doi:10.1159/000214081

Cited by 29 publications

(17 citation statements)

References 47 publications

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“…The mean carbohydrate, fat, and protein intake was 51 E%, 31 E%, and 16 E%, respectively. The concentrations of the inflammatory markers were comparable to values observed among other pregnant populations (Supporting Information Table S1); for example, the median concentration of hsCRP was 2.6 µg/mL (interquartile range, IQR = 2.9), for SAA 761 ng/mL (693), and for IL8 3.3 pg/mL (2.3).…”

Section: Resultssupporting

confidence: 76%

Maternal diet, gestational weight gain, and inflammatory markers during pregnancy

Hrolfsdottir

Schalkwijk

Birgisdóttir

et al. 2016

Obesity

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Section: Resultssupporting

confidence: 76%

Maternal diet, gestational weight gain, and inflammatory markers during pregnancy

Hrolfsdottir

Schalkwijk

Birgisdóttir

et al. 2016

Obesity

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“…This is an inflammatory biomarker, which was shown to increase fourfold in PE in one study (892), was significantly raised in another (882), but not in a third (893). However, it is a well-established (and potent) biomarker for infection/sepsis [e.g., Ref.…”

Section: Proteomic and Similar Biomarkers – Circulating And Placentalmentioning

confidence: 91%

A Dormant Microbial Component in the Development of Preeclampsia

Kell

Kenny

2016

Front. Med.

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Preeclampsia (PE) is a complex, multisystem disorder that remains a leading cause of morbidity and mortality in pregnancy. Four main classes of dysregulation accompany PE and are widely considered to contribute to its severity. These are abnormal trophoblast invasion of the placenta, anti-angiogenic responses, oxidative stress, and inflammation. What is lacking, however, is an explanation of how these themselves are caused. We here develop the unifying idea, and the considerable evidence for it, that the originating cause of PE (and of the four classes of dysregulation) is, in fact, microbial infection, that most such microbes are dormant and hence resist detection by conventional (replication-dependent) microbiology, and that by occasional resuscitation and growth it is they that are responsible for all the observable sequelae, including the continuing, chronic inflammation. In particular, bacterial products such as lipopolysaccharide (LPS), also known as endotoxin, are well known as highly inflammagenic and stimulate an innate (and possibly trained) immune response that exacerbates the inflammation further. The known need of microbes for free iron can explain the iron dysregulation that accompanies PE. We describe the main routes of infection (gut, oral, and urinary tract infection) and the regularly observed presence of microbes in placental and other tissues in PE. Every known proteomic biomarker of “preeclampsia” that we assessed has, in fact, also been shown to be raised in response to infection. An infectious component to PE fulfills the Bradford Hill criteria for ascribing a disease to an environmental cause and suggests a number of treatments, some of which have, in fact, been shown to be successful. PE was classically referred to as endotoxemia or toxemia of pregnancy, and it is ironic that it seems that LPS and other microbial endotoxins really are involved. Overall, the recognition of an infectious component in the etiology of PE mirrors that for ulcers and other diseases that were previously considered to lack one.

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“…Serum amyloid A . This is an inflammatory biomarker, that was shown to increase fourfold in PE in one study [830], was significantly raised in another [819], but not in a third [831]. However, it is a well-established (and potent) biomarker for infection/sepsis (e.g.…”

Section: Proteomic and Similar Biomarkers-circulating And Placentalmentioning

confidence: 99%

A Dormant Microbial Component in the Development of Pre-Eclampsia¹

Kell

Kenny

2016

Preprint

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Pre-eclampsia (PE) is a complex, multi-system disorder that remains a leading cause of morbidity and mortality in pregnancy. Four main classes of dysregulation accompany PE, and are widely considered to contribute to its severity. These are abnormal trophoblast invasion of the placenta, anti-angiogenic responses, oxidative stress, and inflammation. What is lacking, however, is an explanation of how these themselves are caused.We here develop the unifying idea, and the considerable evidence for it, that the originating cause of PE (and of the four classes of dysregulation) is in fact microbial infection, that most such microbes are dormant and hence resist detection by conventional (replication-dependent) microbiology, and that by occasional resuscitation and growth it is they that are responsible for all the observable sequelae, including the continuing, chronic inflammation. In particular, bacterial products such as lipopolysaccharide (LPS), also known as endotoxin, are well known as highly inflammagenic and stimulate an innate (and possibly trained) immune response that exacerbates the inflammation further. The known need of microbes for free iron can explain the iron dysregulation that accompanies PE. We describe the main routes of infection (gut, oral, urinary tract infection) and the regularly observed presence of microbes in placental and other tissues in PE. Every known proteomic biomarker of “pre-eclampsia” that we assessed has in fact also been shown to be raised in response to infection. An infectious component to PE fulfils the Bradford Hill criteria for ascribing a disease to an environmental cause, and suggests a number of treatments, some of which have in fact been shown to be successful.PE was classically referred to as endotoxaemia or toxaemia of pregnancy, and it is ironic that it seems that LPS and other microbial endotoxins really are involved. Overall, the recognition of an infectious component in the aetiology of PE mirrors that for ulcers and other diseases that were previously considered to lack one.Insight, innovation, integrationMany descriptors of pre-eclampsia are widely accepted (e.g. abnormal trophoblast invasion, oxidative stress, inflammation and altered immune response, and anti-angiogenic responses). However, without knowing what causes them, they do not explain the syndrome. The Biological Insight of this manuscript is that there is considerable evidence to the effect that each of these phenomena (hence PE) are caused by the resuscitation of dormant bacteria that shed (known and potent) inflammagens such as LPS, often as a consequence of iron availability. PE is thus seen as a milder form of sepsis. The Technological Innovations come from the use of molecular markers (of microbes and omics more generally, as well as novel markers of coagulopathies) to measure this. The Benefit of Integration comes from bringing together a huge number of disparate observations into a unifying theme.

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Serum Amyloid A Protein and C-Reactive Protein in Normal Pregnancy and Preeclampsia

Cited by 29 publications

References 47 publications

Maternal diet, gestational weight gain, and inflammatory markers during pregnancy

Maternal diet, gestational weight gain, and inflammatory markers during pregnancy

A Dormant Microbial Component in the Development of Preeclampsia

A Dormant Microbial Component in the Development of Pre-Eclampsia¹

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Serum Amyloid A Protein and C-Reactive Protein in Normal Pregnancy and Preeclampsia

Cited by 29 publications

References 47 publications

Maternal diet, gestational weight gain, and inflammatory markers during pregnancy

Maternal diet, gestational weight gain, and inflammatory markers during pregnancy

A Dormant Microbial Component in the Development of Preeclampsia

A Dormant Microbial Component in the Development of Pre-Eclampsia1

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Product

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A Dormant Microbial Component in the Development of Pre-Eclampsia¹