Association between the presence of autoantibodies against adrenoreceptors and severe pre-eclampsia: a pilot study.
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ABSTRACT: Background
Pre-eclampsia is the leading cause of maternal and neonatal morbidity and mortality with incompletely understood etiopathogenesis. The purpose of the current study is to determine whether there is a relationship between the presence of autoantibodies against β1, β2 and α1 adrenoreceptors and severe pre-eclampsia.Methodology/principal findings
Synthetic peptides corresponding to amino acid sequences of the second extracellular loops of β1, β2 and α1 adrenoreceptors were synthesized as antigens to test 34 patients with severe pre-eclampsia, 36 normal pregnancy women and 40 non-pregnant controls for the presence of autoantibodies using enzyme-linked immunosorbent assay. The respective frequencies of autoantibodies against β1, β2 and α1 adrenoreceptors were 50.0% (17/34), 52.9% (18/34) and 55.9% (19/34) in patients with severe pre-eclampsia, 19.4% (7/36) (p = 0.011), 19.4% (7/36) (p = 0.006) and 17.6% (6/36) (p = 0.001) in normal pregnancy women and 10% (4/40), 7.5% (3/40) and 10% (4/40) (p<0.001) in non-pregnant controls. Titers of these autoantibodies were also significantly increased in patients with severe pre-eclampsia. By logistic regression analysis, the presence of these three autoantibodies significantly increased the risk of neonatal death (odds ratio, 13.5; 95% confidence interval, 1.3-141.3; p = 0.030) and long-term neonatal hospitalization (odds ratio, 5.0; 95% confidence interval, 1.3-19.1; p = 0.018). The risk of hypertension and fetal distress were also associated with the presence of these three autoantibodies.Conclusions/significance
This novel pilot study demonstrated for the first time that the presence of autoantibodies against β1, β2 and α1 adrenoreceptors are increased in patients with severe pre-eclampsia. Pregnant women who are positive for the three autoantibodies are at increased risks of neonatal mortality and morbidity. We posit that these autoantibodies may be involved in the pathogenesis of severe pre-eclampsia.
SUBMITTER: Ma G
PROVIDER: S-EPMC3587423 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND: An evidence-based strategy exists to reduce maternal morbidity and mortality associated with severe pre-eclampsia/eclampsia (PE/E), but it may be difficult to implement in low-resource settings. This study examines whether facilities that provide emergency obstetric and newborn care (EmONC) in Afghanistan have the capacity to manage severe PE/E cases. METHODS: A further analysis was conducted of the 2009-10 Afghanistan EmONC Needs Assessment. Assessors observed equipment and supplies available, and services provided at 78 of the 127 facilities offering comprehensive EmONC services and interviewed 224 providers. The providers also completed a written case scenario on severe PE/E. Descriptive statistics were used to summarize facility and provider characteristics. Student t-test, one-way ANOVA, and chi-square tests were performed to determine whether there were significant differences between facility types, doctors and midwives, and trained and untrained providers. RESULTS: The median number of severe PE/E cases in the past year was just 5 (range 0-42) at comprehensive health centers (CHCs) and district hospitals, compared with 44 (range 0-130) at provincial hospitals and 108 (range 32-540) at regional and specialized hospitals (p?<?0.001). Most facilities had the drugs and supplies needed to treat severe PE/E, including the preferred anticonvulsant, magnesium sulfate (MgSO4). One-third of the smallest facilities and half of larger facilities reported administering a second-line drug, diazepam, in some cases. In the case scenario, 96% of doctors and 89% of midwives recognized that MgSO4 should be used to manage severe PE/E, but 42% of doctors and 58% of midwives also thought diazepam had a role to play. Providers who were trained on the use of MgSO4 scored significantly higher than untrained providers on six of 20 items in the case scenario. Providers at larger facilities significantly outscored those at smaller facilities on five items. There was a significant difference between doctors and midwives on only one item: continued use of anti-hypertensives after convulsions are controlled. CONCLUSIONS: Drugs and supplies needed to treat severe PE/E are widely available at EmONC facilities in Afghanistan, but providers lack knowledge in some areas, especially concerning the use of MgSO4 and diazepam. Providers who have specialized training or work at larger facilities are better at managing cases of severe PE/E. The findings suggest a need to clarify service delivery guidelines, offer refresher training, and reinforce best practices with supervision and reinforcement.
| S-EPMC3852136 | biostudies-literature
Project description:BackgroundPre-eclampsia is the most common complication occurring during pregnancy. In the majority of cases, it is concurrent with other pathologies in a comorbid manner (frequent co-occurrences in patients), such as diabetes mellitus, gestational diabetes and obesity. Providing bronchial asthma, pulmonary tuberculosis, certain neurodegenerative diseases and cancers as examples, we have shown previously that pairs of inversely comorbid pathologies (rare co-occurrences in patients) are more closely related to each other at the molecular genetic level compared with randomly generated pairs of diseases. Data in the literature concerning the causes of pre-eclampsia are abundant. However, the key mechanisms triggering this disease that are initiated by other pathological processes are thus far unknown. The aim of this work was to analyse the characteristic features of genetic networks that describe interactions between comorbid diseases, using pre-eclampsia as a case in point.ResultsThe use of ANDSystem, Pathway Studio and STRING computer tools based on text-mining and database-mining approaches allowed us to reconstruct associative networks, representing molecular genetic interactions between genes, associated concurrently with comorbid disease pairs, including pre-eclampsia, diabetes mellitus, gestational diabetes and obesity. It was found that these associative networks statistically differed in the number of genes and interactions between them from those built for randomly chosen pairs of diseases. The associative network connecting all four diseases was composed of 16 genes (PLAT, ADIPOQ, ADRB3, LEPR, HP, TGFB1, TNFA, INS, CRP, CSRP1, IGFBP1, MBL2, ACE, ESR1, SHBG, ADA). Such an analysis allowed us to reveal differential gene risk factors for these diseases, and to propose certain, most probable, theoretical mechanisms of pre-eclampsia development in pregnant women. The mechanisms may include the following pathways: [TGFB1 or TNFA]-[IL1B]-[pre-eclampsia]; [TNFA or INS]-[NOS3]-[pre-eclampsia]; [INS]-[HSPA4 or CLU]-[pre-eclampsia]; [ACE]-[MTHFR]-[pre-eclampsia].ConclusionsFor pre-eclampsia, diabetes mellitus, gestational diabetes and obesity, we showed that the size and connectivity of the associative molecular genetic networks, which describe interactions between comorbid diseases, statistically exceeded the size and connectivity of those built for randomly chosen pairs of diseases. Recently, we have shown a similar result for inversely comorbid diseases. This suggests that comorbid and inversely comorbid diseases have common features concerning structural organization of associative molecular genetic networks.
| S-EPMC4407242 | biostudies-literature
Project description:Pre-eclampsia affects approximately 5% of pregnancies and remains a leading cause of maternal and neonatal mortality and morbidity in the United States and the world. The clinical hallmarks of this maternal disorder include hypertension, proteinuria, endothelial dysfunction and placental defects. Advanced-stage clinical symptoms include cerebral hemorrhage, renal failure and the HELLP (hemolysis, elevated liver enzymes and low platelets) syndrome. An effective treatment of pre-eclampsia is unavailable owing to the poor understanding of the pathogenesis of the disease. Numerous recent studies have shown that women with pre-eclampsia possess autoantibodies, termed AT(1)-AAs, that bind and activate the angiotensin II receptor type 1a (AT(1) receptor). We show here that key features of pre-eclampsia, including hypertension, proteinuria, glomerular endotheliosis (a classical renal lesion of pre-eclampsia), placental abnormalities and small fetus size appeared in pregnant mice after injection with either total IgG or affinity-purified AT(1)-AAs from women with pre-eclampsia. These features were prevented by co-injection with losartan, an AT(1) receptor antagonist, or by an antibody neutralizing seven-amino-acid epitope peptide. Thus, our studies indicate that pre-eclampsia may be a pregnancy-induced autoimmune disease in which key features of the disease result from autoantibody-induced angiotensin receptor activation. This hypothesis has obvious implications regarding pre-eclampsia screening, diagnosis and therapy.
| S-EPMC3267158 | biostudies-literature
Project description:BackgroundPre-eclampsia with severe features (PEC) is a pregnancy-specific syndrome characterized by severe hypertension and end-organ dysfunction, and is associated with short-term adverse cardiovascular events, including heart failure, pulmonary edema, and stroke.ObjectivesThe authors aimed to characterize the short-term echocardiographic, clinical, and laboratory changes in women with PEC, focusing on right ventricular (RV) systolic pressure (RVSP) and echocardiographic-derived diastolic, systolic, and speckle tracking parameters.MethodsIn this prospective observational study, the authors recruited 63 women with PEC and 36 pregnant control patients.ResultsThe PEC cohort had higher RVSP (31.0 ± 7.9 mm Hg vs. 22.5 ± 6.1 mm Hg; p < 0.001) and decreased global RV longitudinal systolic strain (RVLSS) (-19.6 ± 3.2% vs. -23.8 ± 2.9% [p < 0.0001]) when compared with the control cohort. For left-sided cardiac parameters, there were differences (p < 0.001) in mitral septal e' velocity (9.6 ± 2.4 cm/s vs. 11.6 ± 1.9 cm/s), septal E/e' ratio (10.8 ± 2.8 vs. 7.4 ± 1.6), left atrial area size (20.1 ± 3.8 cm2 vs. 17.3 ± 2.9 cm2), and posterior and septal wall thickness (median [interquartile range]: 1.0 cm [0.9 to 1.1 cm] vs. 0.8 cm [0.7 to 0.9 cm], and 1.0 cm [0.8 to 1.2 cm] vs. 0.8 cm [0.7 to 0.9 cm]). Eight women (12.7%) with PEC had grade II diastolic dysfunction, and 6 women (9.5%) had peripartum pulmonary edema.ConclusionsWomen with PEC have higher RVSP, higher rates of abnormal diastolic function, decreased global RVLSS, increased left-sided chamber remodeling, and higher rates of peripartum pulmonary edema, when compared with healthy pregnant women.
| S-EPMC8136241 | biostudies-literature
Project description:This meta-analysis was performed in order to determine the associations between the estrogen receptor α (ESR1) gene PvuII site (-397T/C, rs2234693) and XbaI site (-351A/G, rs9340799) polymorphisms with severe and mild pre-eclampsia. Eligible studies were identified by searching PubMed, Medline, Embase, China National Knowledge Infrastructure (CNKI), and WanFang databases until May 2018. The pooled odds ratio (OR) and 95% confidence interval (CI) were used to calculate the associations. Six articles (consisting of seven studies; one article was considered as two separate studies with two different subpopulations) investigated the ESR1 gene PvuII -397T/C and XbaI -351A/G polymorphisms in severe and mild pre-eclampsia patients and included controls. The pooled results indicated an increased risk of severe pre-eclampsia for the XbaI -351A/G polymorphism (OR = 1.67, 95% CI = 1.10-2.25, P=0.017 for GG compared with AA+GA; OR = 1.81, 95% CI = 1.17-2.82, P=0.008 for GG compared with GA). The GG genotype of the ESR1 XbaI polymorphism could be a genetic risk factor for severe pre-eclampsia susceptibility. However, the ESR1 gene PvuII -397T/C polymorphism was not significantly associated with the risk of severe pre-eclampsia, and there was no association between mild pre-eclampsia and the ESR1 gene PvuII -397T/C and XbaI -351A/G polymorphisms separately. The current meta-analysis indicates that the ESR1 XbaI genetic polymorphism may be associated with severe pre-eclampsia. However, there was no association of the ESR1 gene PvuII and XbaI polymorphisms with the risk of mild pre-eclampsia. Owing to the low statistical power, the results may not be sufficiently robust and this conclusion should be interpreted cautiously, which highlights the requirement for large-scale and high-quality studies in this field.
| S-EPMC6367125 | biostudies-literature
Project description:ObjectiveTo test the hypothesis that pre-eclampsia is a risk factor for cerebral palsy mediated through preterm birth and being born small for gestational age.DesignPopulation based cohort study.SettingClinical data from the Norwegian Cerebral Palsy Registry were linked with perinatal data prospectively recorded by the Medical Birth Registry of Norway.ParticipantsAll singleton babies who survived the neonatal period during 1996-2006 (849 children with cerebral palsy and 616,658 control children).Main outcome measuresCerebral palsy and cerebral palsy subtypes.ResultsChildren exposed to pre-eclampsia had an excess risk of cerebral palsy (unadjusted odds ratio 2.5, 95% confidence interval 2.0 to 3.2) compared with unexposed children. Among children born at term (≥ 37 weeks), exposure to pre-eclampsia was not associated with an excess risk of cerebral palsy in babies not born small for gestational age (1.2, 0.7 to 2.0), whereas children exposed to pre-eclampsia and born small for gestational age had a significantly increased risk of cerebral palsy (3.2, 1.5 to 6.7). Non-small for gestational age babies born very preterm (<32 weeks) and exposed to pre-eclampsia had a reduced risk of cerebral palsy compared with unexposed children born at the same gestational age (0.5, 0.3 to 0.8), although the risk was not statistically significantly reduced among children exposed to pre-eclampsia and born small for gestational age (0.7, 0.4 to 1.3). Exposure to pre-eclampsia was not associated with a specific cerebral palsy subtype.ConclusionsExposure to pre-eclampsia was associated with an increased risk of cerebral palsy, and this association was mediated through the children being born preterm or small for gestational age, or both. Among children born at term, pre-eclampsia was a risk factor for cerebral palsy only when the children were small for gestational age.
| S-EPMC3706637 | biostudies-literature
Project description:BackgroundIgG-class autoantibodies to N-Methyl-D-Aspartate (NMDA)-type glutamate receptors define a novel entity of autoimmune encephalitis. Studies examining the prevalence of NMDA IgA/IgM antibodies in patients with Parkinson disease with/without dementia produced conflicting results. We measured NMDA antibodies in a large, well phenotyped sample of Parkinson patients without and with cognitive impairment (n = 296) and controls (n = 295) free of neuropsychiatric disease. Detailed phenotyping and large numbers allowed statistically meaningful correlation of antibody status with diagnostic subgroups as well as quantitative indicators of disease severity and cognitive impairment.MethodsNMDA antibodies were analysed in the serum of patients and controls using well established validated assays. We used anti-NMDA antibody positivity as the main independent variable and correlated it with disease status and phenotypic characteristics.ResultsThe frequency of NMDA IgA/IgM antibodies was lower in Parkinson patients (13%) than in controls (22%) and higher than in previous studies in both groups. NMDA IgA/IgM antibodies were neither significantly associated with diagnostic subclasses of Parkinson disease according to cognitive impairment, nor with quantitative indicators of disease severity and cognitive impairment. A positive NMDA antibody status was positively correlated with age in controls but not in Parkinson patients.ConclusionIt is unlikely albeit not impossible that NMDA antibodies play a significant role in the pathogenesis or progression of Parkinson disease e.g. to Parkinson disease with dementia, while NMDA IgG antibodies define a separate disease of its own.
| S-EPMC6446289 | biostudies-literature
Project description:The etiology of preeclampsia, a hypertensive disorder of human pregnancy, remains unknown. We addressed fetal sex selection and the suggestive role of fetal HLA-G and related genes, regulating maternal immune responses, in preeclampsia pathogenesis. We assessed birth sex ratios, weights, and seasonality of preeclampsia among 1.79 million births in Finland. We studied haplotypes of HLA-G 3’ untranslated region (UTR), regulating HLA-G expression, in 1000 Genomes series and in a preeclampsia cohort (n=1249). We quantified placental (n=163) mRNA expression of 136 genes, studied HLA-G and IFNα protein expression by immunohistochemistry, and measured maternal and fetal circulating IFNα levels by ELISA. Population-level data showed loss of male fetuses as a characteristic of preeclampsia. As a potential contributor to immune-mediated loss, we found balancing selection at HLA-G 3’UTR modulating sex ratio, and association of HLA-G 3’UTR haplotypes with placental HLA-G expression. HLA-G and its receptors were downregulated in preeclampsia placentas, and surprisingly, interferon alpha-1 (IFNA1) was highly upregulated. IFNA1 and HLA-G distinguished preeclampsia better than placental FLT1 expression. Fetal but not maternal circulating IFNα, produced by trophoblasts, showed association with maternal hypertension and fetal growth restriction. We uncover the link between placental HLA-G expression and human birth sex ratio. We propose that preeclampsia shares, through reduced HLA-G mediated immunotolerance, the mechanism needed to fight placental viral infections and malaria in evolution. IFNα upregulation in preeclampsia placenta, together with its known actions upstream of inflammatory genes, encourages testing IFNα inhibitors and especially the pregnancy-approved antimalarial hydroxichloroquine in treatment of preeclampsia.
2019-11-25 | GSE125460 | GEO
Project description:BackgroundStudies have suggested controversial results regarding a possible association between pre-eclampsia (PE) and periodontal disease (PD) and no meta-analysis has been performed to clarify this issue.MethodsA literature search of electronic databases was performed for articles published through March 24, 2013, followed by a manual search of several dental and medical journals. The meta-analysis was conducted according to the recommendations of the Cochrane Collaboration and PRISMA. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Heterogeneity was assessed with the χ(2)-based Cochran Q test and I(2) statistic. The level of significance was set at P <0.05.ResultsFifteen studies were included, including three cohort and 12 case-control studies. A positive association was found between PE and PD (OR 2.17, 95% CI 1.38-3.41, P = 0.0008). However, a high and significant heterogeneity was found (χ(2) = 62.42, P<0.00001, I(2) = 75%). In most cases, subgroup analysis had low power to detect significant differences between PE and non-PE groups.ConclusionBased on the findings of the meta-analysis, PD appears to be a possible risk factor for PE. However, given the important differences in the definitions and diagnoses of PD and PE among the studies, as well as their lack of good methodological quality, future trials are needed to confirm the results of the present meta-analysis.
| S-EPMC3747173 | biostudies-literature
Project description:PurposeEosinophils are frequently found in atopic dermatitis (AD) and chronic spontaneous urticaria (CSU) that release eosinophil peroxidase (EPX) and eosinophil cationic protein (ECP). Continuous exposure to these proteins could trigger an autoimmune response which may contribute to the pathogenesis and severity of skin inflammation. In this study, we investigate the immunoglobulin E (IgE) response against eosinophil proteins in CSU and AD.MethodsWe recruited patients with severe AD, severe CSU and healthy subjects to explore the presence of IgE autoantibodies and cross-reactivity against EPX, ECP and thyroid peroxidase (TPO). The potential cross-reactive epitopes among the peroxidase family were determined using in silico tools.ResultsThe frequencies of anti-EPX IgE (28.8%) and anti-ECP IgE (26.6%) were higher in the AD group, and anti-TPO IgE was higher in the CSU group (27.2%). In the CSU group, there was a correlation between the anti-EPX IgE and anti-TPO IgE levels (r = 0.542, P < 0.001); TPO inhibited 42% of IgE binding to EPX, while EPX inhibited 59% of IgE binding to TPO, suggesting a cross-reactivity with EPX as a primary sensitizer. There was greater inhibition when we used a pool of sera CSU and AD, TPO inhibited 52% of IgE binding to EPX, while EPX inhibited 78% of IgE binding to TPO. In silico analysis showed a possible shared epitope in the peroxidase protein family.ConclusionsIgE against eosinophil proteins may contribute to chronic inflammation in patients with AD and CSU. Cross-reactivity between EPX and TPO could explain thyroid problems in CSU patients.
| S-EPMC8419645 | biostudies-literature