Smooth Muscle Antibodies in Pre-Eclampsia of Pregnancy

Pietarinen, Ilmo; Kivinen, Seppo; Ylöstalo, Pekka; Mäkitalo, R; Laakso, L

doi:10.1159/000299502

Cited by 9 publications

(5 citation statements)

References 9 publications

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“…Other investigators have observed a significant increase in smooth muscle autoantibodies in patients with hypertensive disorders of pregnancy (19,20). Smooth muscle autoantibodies were reported to be increased in patients with threatened abortions and spontaneous abortions compared with those with uncomplicated pregnancies (21).…”

Section: Autoantibody Studiesmentioning

confidence: 92%

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Risk Factors for Gestational Diabetes in Black Population

Bell

Barger²,

Go³

et al. 1990

Diabetes Care

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In a long-term longitudinal study of gestational diabetes mellitus in Black women, risk factors that were identified were age, obesity, a family history of diabetes, and the presence of hypertension. Poor predictors were a history of a previous large-for-date infant, parity, and age at first pregnancy. The prevalence of smooth muscle and nuclear autoantibodies was higher in gestational diabetic subjects. Gestational diabetic subjects who required insulin for glycemic control were more obese, had a lower frequency of the Bf-F phenotype and a higher frequency of the Bf-F1 phenotype, and had a lower frequency of the type 2 allele at the polymorphic locus adjacent to the insulin gene. Restriction-fragment-length polymorphisms flanking the insulin and apolipoprotein A-I and C-III genes, although not associated with gestational diabetes mellitus, may be associated with hyperlipidemia and subsequent atherosclerosis.

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Section: Autoantibody Studiesmentioning

confidence: 92%

“…In addition, autoantibodies have been reported to be increased in preeclampsia (19,20) and spontaneous abortions (21-23).…”

Section: Autoantibody Studiesmentioning

confidence: 99%

Risk Factors for Gestational Diabetes in Black Population

Bell

Barger²,

Go³

et al. 1990

Diabetes Care

View full text Add to dashboard Cite

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“…To this end, we note that PE has also been associated with antibodies to angiotensin receptors (577–590), to smooth muscle (591, 592) [such blocking may be anti-inflammatory (593–595)], to adrenoceptors (596), to the M2 muscarinic receptor (597), and to Th17 (598) [and see Ref. (599)].…”

Section: Effects Of Lps and Other Microbial Antigens On Disrupting Trmentioning

confidence: 99%

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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“…In many cases, the actual (and possibly microbial) antigens are unknown, and clearly the microbial elicitation of antibodies to anything that might contribute to PE points to multiple potential origins. To this end, we note that PE has also been associated with antibodies to angiotensin receptors [553–566], to smooth muscle [567; 568] (such blocking may be anti-inflammatory [569–571]), to adrenoceptors [572], to the M2 muscarinic receptor [573], and to Th17 [574](and see [575]). It is not unreasonable that epitope scanning of the antibody targets coupled to comparative sequence analysis of potential microbes might light up those responsible.…”

Section: Effects Of Lps and Other Microbial Antigens On Disrupting Trmentioning

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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Smooth Muscle Antibodies in Pre-Eclampsia of Pregnancy

Cited by 9 publications

References 9 publications

Risk Factors for Gestational Diabetes in Black Population

Risk Factors for Gestational Diabetes in Black Population

A Dormant Microbial Component in the Development of Preeclampsia

A Dormant Microbial Component in the Development of Pre-Eclampsia¹

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Smooth Muscle Antibodies in Pre-Eclampsia of Pregnancy

Cited by 9 publications

References 9 publications

Risk Factors for Gestational Diabetes in Black Population

Risk Factors for Gestational Diabetes in Black Population

A Dormant Microbial Component in the Development of Preeclampsia

A Dormant Microbial Component in the Development of Pre-Eclampsia1

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A Dormant Microbial Component in the Development of Pre-Eclampsia¹