scholarly journals Antibodies to Pneumococcal Proteins PhtD, CbpA, and LytC in Filipino Pregnant Women and Their Infants in Relation to Pneumococcal Carriage

2009 ◽  
Vol 16 (6) ◽  
pp. 916-923 ◽  
Author(s):  
Emma Holmlund ◽  
Beatriz Quiambao ◽  
Jukka Ollgren ◽  
Teija Jaakkola ◽  
Cécile Neyt ◽  
...  

ABSTRACTThis study focuses on the immunogenicity of the following three pneumococcal vaccine candidate proteins in Filipino infants, all inducing protection in animal models: pneumococcal histidine triad protein D (PhtD), choline binding protein A (CbpA), and the lysozyme LytC. The immunoglobulin G antibody concentrations to PhtD, its putative, protective, and exposed C-terminal fragment (PhtD C), CbpA, and LytC were measured by enzyme immunoassay in 52 serum samples from pregnant women, 39 cord blood samples, and consecutive serum samples (n= 263) from 52 newborns between 6 weeks and 10 months of age scheduled to be taken at six time points. A nasopharyngeal swab to detect pneumococcal carriage was taken parallel to the serum samples. The antibody concentrations in the cord blood samples were similar to those in the samples from the mothers. In infant sera, the geometric mean antibody concentrations (GMCs) for all three proteins decreased until the age of 18 weeks and started to increase after that age, suggesting that the infants' own antibody production started close to the age of 4 to 5 months. The increase in GMCs by age, most clear-cut for CbpA, was associated with pneumococcal carriage. Anti-PhtD concentrations were higher than anti-PhtD C concentrations but correlated well (rof 0.89 at 10.5 months), suggesting that antibodies are directed to the supposedly exposed and protective C-terminal part of PhtD. Our results show that young children are able to develop an antibody response to PhtD, CbpA, and LytC and encourage the development of pneumococcal protein vaccines for this age group.

PEDIATRICS ◽  
1982 ◽  
Vol 69 (2) ◽  
pp. 188-192
Author(s):  
Guillermo R. Mendoza ◽  
Kiminobu Minagawa ◽  
Francine B. Orner ◽  
E. Richard Stiehm

Cord basophil preparations from 53 term neonates were studied for various factors affecting immediate hypersensitivity reactions including: basophil IgE receptor density and histamine releasability following incubation with calcium ionophore A23187, zymosan-activated serum (C5a), and anti-IgE. Basophil histamine content (geometric mean, 0.4 pg/basophil, with content in 14/28 cord blood samples below 0.2 pg/cell) is considerably below that of atopic and nonatopic individuals (geometric mean, 2.3 pg/basophil). Histamine release is normal with both A23187 (range 33% to 88%) and C5a (range 11% to 58%). Normal release with anti-IgE was shown in five of nine cord blood samples (range 13% of 52%), but four of five cell preparations required IgE preincubation. Indirect evidence indicates that basophils from newborns contain less than 30,000 total IgE receptors /cell. IgE-mediated histamine release in basophils from newborns is minimized by suboptimal IgE binding. Optimal IgE binding is not favored in basophils from neonates because of low serum IgE and low IgE receptor density. Serum IgE and IgE receptors increase to a variable degree as the child grows older and may determine the clinical onset of allergic disease.


2020 ◽  
Vol 27 (1) ◽  
Author(s):  
Maria García-Ricobaraza ◽  
Mercedes García-Bermúdez ◽  
Francisco J. Torres-Espinola ◽  
M. Teresa Segura Moreno ◽  
Mathieu N. Bleyere ◽  
...  

Abstract Background Peroxisome proliferator activated receptor gamma (PPARG) belongs to the nuclear receptor superfamily functioning as transcription factors to regulate cellular differentiation, development and metabolism. Moreover, it has been implicated in the regulation of lipid metabolism, as well as the maturation of monocytes/macrophages and the control of inflammatory reactions. The aim of this study was to evaluate the relationship between the Pro12Ala (rs1808212) PPARG gene polymorphism on immune molecular and cellular components in mothers and their offspring participating in the PREOBE study. Methods DNA from maternal venous blood samples at 24, 34 and 40 gestational weeks, plus cord blood samples was extracted. Pro12Ala PPARG polymorphism genotyping was performed, and immune system markers were analyzed by flow cytometry. Results Study findings revealed no effect of rs1808212 PPARG genotypes on innate immune parameters in mothers and their offspring; however, CD4 + /CD8 + ratio were decreased at 24 and 34 weeks in pregnant women carrying the CG (Pro12Ala) rs1808212 polymorphism, (p = 0,012 and p = 0,030; respectively). Only CD19 levels in peripheral blood were significantly higher at delivery in pregnant women carrying the CC (Pro12Pro) genotype (p ≤ 0.001). Moreover, there were statistically significant differences in leukocytes and neutrophils maternal levels at 34 weeks of gestation, being lower in carriers of Pro12Ala genotype (p = 0.028 and p = 0.031, respectively). Conclusions Results suggest that Pro12Ala PPARG polymorphism may have an effect on some cell and immune parameters in pregnant women during pregnancy and at time of delivery. However, newborn innate immune system does not seems to be influenced by PPARG Pro12Ala polymorphism in cord blood.


2019 ◽  
Vol 105 (4) ◽  
pp. e1085-e1092
Author(s):  
Mengdi Lu ◽  
Bruce W Hollis ◽  
Vincent J Carey ◽  
Nancy Laranjo ◽  
Ravinder J Singh ◽  
...  

Abstract Context Vitamin D (VD) deficiency in pregnancy and the neonatal period has impacts on childhood outcomes. Maternal VD sufficiency is crucial for sufficiency in the neonate, though the effect of early versus late pregnancy 25-hydroxy-vitamin D (25(OH)D) levels on neonatal levels is unknown. Furthermore, chemiluminescence immunoassays (CLIAs) are widely used, though their validity in measuring 25(OH)D specifically in cord blood specimens has not been established. Objective To assess the validity of a CLIA in the measurement of cord blood 25(OH)D and to evaluate maternal determinants of neonatal 25(OH)D, including early versus late pregnancy 25(OH)D levels. Design This is an ancillary analysis from the Vitamin D Antenatal Asthma Reduction Trial (VDAART), a randomized, double-blinded, placebo-controlled study. Participants and Intervention A total of 881 pregnant women at high risk of having offspring asthma were randomized to receive VD supplementation or placebo. Serum samples were collected from mothers in early and late pregnancy and from offspring cord blood at birth. 25(OH)D levels were assayed by CLIA in all maternal and offspring samples and by LC-MS/MS in all offspring samples and a subset of 200 maternal third trimester samples. Results Cord blood 25(OH)D levels were higher as measured by CLIA (mean 37.13 ng/mL [SD 18.30]) than by LC-MS/MS (mean 23.54 ng/mL [SD 11.99]), with a mean positive bias of 13.54 ng/mL (SD 12.92) by Bland-Altman analysis. This positive bias in measurement by CLIA was not observed in maternal samples. Third trimester 25(OH)D was a positive determinant of neonatal 25(OH)D levels. Conclusion Chemiluminescence immunoassays overestimate 25(OH)D levels in human cord blood samples, an effect not observed in maternal blood samples. The quantification of 25(OH)D by CLIA should therefore not be considered valid when assayed in cord blood samples. Third trimester, but not first trimester, maternal 25(OH)D is one of several determinants of neonatal 25(OH)D status.


2005 ◽  
Vol 51 (1) ◽  
pp. 75-83 ◽  
Author(s):  
Qiu-Ping Qin ◽  
Saara Kokkala ◽  
Juha Lund ◽  
Natalia Tamm ◽  
Liisa-Maria Voipio-Pulkki ◽  
...  

Abstract Background: In the blood of pregnant women, pregnancy-associated plasma protein A (PAPP-A) is present as a covalent complex with the proform of eosinophil major basic protein (proMBP). Recently, increased serum concentrations of PAPP-A have been found in acute coronary syndromes (ACS). The aim of this study was to investigate whether the circulating PAPP-A in ACS is the same as that in pregnancy. Methods: We developed two time-resolved immunofluorometric assays based on a relative epitope map constructed by the use of 17 monoclonal antibodies. One assay, which measured total PAPP-A, used two PAPP-A subunit-specific antibodies. The other assay, which measured PAPP-A/proMBP complex, used one proMBP subunit-specific antibody and one PAPP-A subunit-specific antibody. Serum samples from four patients with myocardial infarction (MI), three pregnant women in their first trimester, and one in her third trimester were fractionated by gel filtration on a Superose™ 6 precision column. The two assays were used to analyze fractions obtained by gel filtration as well as serum samples serially collected from four other MI patients. Results: Pregnancy-related PAPP-A was eluted as a single peak with a molecular mass of ∼700 kDa, whereas ACS-related PAPP-A was also eluted as a single peak but with a molecular mass of ∼530 kDa. Pregnancy-related PAPP-A was detected equally by the two assays, whereas increased ACS-related PAPP-A was detected only by the assay for total PAPP-A. Conclusions: Our results provide the first evidence that circulating ACS-related PAPP-A is different from circulating pregnancy-related PAPP-A in that it is not complexed with proMBP. These findings provide a solid foundation for the design of immunoassays to accurately measure atherosclerosis-associated plasma protein A in the circulation.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S970-S970 ◽  
Author(s):  
Beate Schmoele-Thoma ◽  
Ann R Falsey ◽  
Edward E Walsh ◽  
Kena Swanson ◽  
Agnieszka Zareba ◽  
...  

Abstract Background The respiratory syncytial virus (RSV) fusion glycoprotein (F) is a molecule that fuses the viral and host cell membranes during virus entry as it rearranges from a meta-stable prefusion to a stable postfusion conformation. Using structure-guided design, Pfizer engineered a prefusion RSV F subunit vaccine antigen with stable and well-characterized conformational homogeneity. Methods We report results of a 1,182 subject, first-in-human, phase 1/2, placebo-controlled, randomized, observer-blind, dose-finding study to describe the safety, tolerability, and immunogenicity of the Pfizer RSV vaccine candidate in healthy men and non-pregnant women from 18 to 85 years of age. The study compares three dosages of the vaccine candidate, with and without aluminum hydroxide, and also compares immunization with the RSV vaccine candidate alone or concomitantly with influenza vaccine. The study is ongoing to collect antibody persistence and additional safety data. Results The data, which are currently available for the 18- to 49-year-old subgroup, demonstrate an excellent safety and tolerability profile. Immunization with the various formulations of the vaccine candidate elicited RSV 50% neutralization titer geometric mean fold rises (GMFRs) of 10.6–17.2 for subgroup A and 10.4–19.8 for subgroup B, measured one month after immunization, with evidence of a dose–response. Conclusion The 10- to 20-fold increases in neutralizing antibody titers elicited by this vaccine with a stable prefusion F antigen represent a step change relative to the historical performance of vaccine candidates, such as Wyeth’s PFP, with F antigens that were not stabilized in the prefusion conformation (Simoes et al., Vaccine 20:954–60, 2002). The data strongly support development of this vaccine candidate to prevent RSV disease in infants, by immunizing pregnant women, and to prevent RSV disease in older adults, by direct immunization. Disclosures All authors: No reported disclosures.


2020 ◽  
Vol 37 (10) ◽  
pp. 1055-1060 ◽  
Author(s):  
Ziyi Yang ◽  
Yi Liu

Objective The aim of this study is to summarize currently available evidence on vertical transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Study Design A systematic review was conducted following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analysis Statement. Results A total of 22 studies comprising 83 neonates born to mothers diagnosed with coronavirus disease 2019 were included in the present systematic review. Among these neonates, three were confirmed with SARS-CoV-2 infection at 16, 36, and 72 hours after birth, respectively, by nasopharyngeal swab real-time polymerase chain reaction (RT-PCR) tests; another six had elevated virus-specific antibody levels in serum samples collected after birth, but negative RT-PCR test results. However, without positive RT-PCR tests of amniotic fluid, placenta, or cord blood, there is a lack of virologic evidence for intrauterine vertical transmission. Conclusion There is currently no direct evidence to support intrauterine vertical transmission of SARS-CoV-2. Additional RT-PCR tests on amniotic fluid, placenta, and cord blood are needed to ascertain the possibility of intrauterine vertical transmission. For pregnant women infected during their first and second trimesters, further studies focusing on long-term outcomes are needed. Key Points


2009 ◽  
Vol 13 (3) ◽  
pp. 331-337 ◽  
Author(s):  
Emeir M Duffy ◽  
Maxine P Bonham ◽  
Julie MW Wallace ◽  
Chin-Kuo Chang ◽  
Paula J Robson ◽  
...  

AbstractObjectiveTo establish the Fe status of pregnant women and their neonates in the Republic of Seychelles.DesignA prospective study.SettingRepublic of Seychelles.SubjectsPregnant women were recruited and blood samples taken at enrolment and post-delivery along with cord blood samples. Ferritin and soluble transferrin receptor (sTfR) were measured in maternal (n220) and cord blood (n123) samples.ResultsMaternal Fe deficiency (ferritin < 15 ng/ml, sTfR > 28 nmol/l) was present in 6 % of subjects at enrolment and in 20 % at delivery. There was no significant decrease in maternal ferritin. A significant increase in sTfR was observed between enrolment and delivery (P< 0·001). Maternal BMI and use of Fe supplements at 28 weeks’ gestation were associated with improved maternal Fe status at delivery, whereas parity had a negative effect on sTfR and ferritin at delivery.ConclusionsFe status of pregnant Seychellois women was, on average, within normal ranges. The incidence of Fe deficiency throughout pregnancy in this population was similar to that in a Westernised population. Increased awareness of the importance of adequate Fe intake during pregnancy, particularly in multiparous women, is warranted.


2014 ◽  
Vol 58 (6) ◽  
pp. 3504-3513 ◽  
Author(s):  
Mohammed H. Elkomy ◽  
Pervez Sultan ◽  
David R. Drover ◽  
Ekaterina Epshtein ◽  
Jeffery L. Galinkin ◽  
...  

ABSTRACTThe objectives of this work were (i) to characterize the pharmacokinetics of cefazolin in pregnant women undergoing elective cesarean delivery and in their neonates; (ii) to assess cefazolin transplacental transmission; (iii) to evaluate the dosing and timing of preoperative, prophylactic administration of cefazolin to pregnant women; and (iv) to investigate the impact of maternal dosing on therapeutic duration and exposure in newborns. Twenty women received 1 g of cefazolin preoperatively. Plasma concentrations of total cefazolin were analyzed from maternal blood samples taken before, during, and after delivery; umbilical cord blood samples obtained at delivery; and neonatal blood samples collected 24 h after birth. The distribution volume of cefazolin was 9.44 liters/h. The values for pre- and postdelivery clearance were 7.18 and 4.12 liters/h, respectively. Computer simulations revealed that the probability of maintaining free cefazolin concentrations in plasma above 8 mg/liter during scheduled caesarean surgery was <50% in the cord blood when cefazolin was administered in doses of <2 g or when it was administered <1 h before delivery. Therapeutic concentrations of cefazolin persisted in neonates >5 h after birth. Cefazolin clearance increases during pregnancy, and larger doses are recommended for surgical prophylaxis in pregnant women to obtain the same antibacterial effect as in nonpregnant patients. Cefazolin has a longer half-life in neonates than in adults. Maternal administration of up to 2 g of cefazolin is effective and produces exposure within clinically approved limits in neonates.


Author(s):  
Sharanya Satish ◽  
K. B. Suma ◽  
Madhu B. ◽  
Sujatha M. S.

Background: Hypertensive disorder affects 10-12% of pregnancies. Identifying women, who are at risk is conducive to prompt gestational management. PAPP-A is a protein complex produced by the developing trophoblasts. Low levels of PAPP-A at 10–14 weeks is a marker of impaired placentation and a smaller placental mass. Doppler imaging permits non-invasive evaluation of the uteroplacental circulation and is invaluable in the management of high-risk pregnancies. The uterine artery Doppler screening identifies patients at risk for developing preeclampsia. To study the association of PAPP-A and the uterine artery Doppler changes as predictor of pre-eclampsia in pregnant women at 11-14 weeks of gestation.Methods: This was a prospective study of 150 pregnant women presenting at 11-14 weeks of gestation for a prenatal check-up. After considering the inclusion and exclusion criteria, serum samples for PAPP-A were assayed. Ultrasound Doppler was used to obtain uterine artery flow velocity waveforms and mean pulsatility index and resistance index of uterine arteries were calculated. Cases were followed up till term and observed for development of pre-eclampsia.Results: 48.6% had low serum PAPP-A levels, in which 77% developed PE. The Mean PI and RI is 2.34±1.16 and 0.58±0.1 respectively. 30% women with abnormal PI values and 24% of women with abnormal RI values developed PE.Conclusions: The combination of maternal history with low serum PAPP-A levels and abnormal uterine artery Doppler at 11-14 weeks can be used as predictor of pre-eclampsia.


2004 ◽  
Vol 12 (4) ◽  
pp. 200-202 ◽  
Author(s):  
Miroslava Stankovic ◽  
Gordana Joksic ◽  
Marija Guc-Scekic

BACKGROUND: This study provides the data regarding monitoring of population using CB-micronuclei assay in the period 1995-2001 in Serbia. The target groups consisted of 45 pregnant women of mean age 34.3(6.56) years, unaware of being exposed to chemicals drugs or other substances and undergoing cordocentesis. The incidence of micronuclei (MN) in peripheral blood lymphocytes and in fetal cord blood lymphocytes was analyzed. METHODS: The study was carried out on cultures of PHA-stimulated blood lymphocytes. Three drops of blood samples ware added into 5ml RPMI-1640 (Gibco) medium supplemented with 15% of calf serum and PHA (Gibco, 2.5?g/ml). For micronuclei preparation the cytokinesis block method was used (Fenech et al., 1993). RESULTS: The results of the study showed that in the year 1995, the incidence of micronuclei in pregnant women was 9.61(3.26) per 1000 binucleated (BN) cells, and 3.74(1.60) in cord blood samples per 1000 BN cells, respectively. In 2000 the incidence of micronuclei in study group was 28.26(7.87) per 1000 BN cells, and in cord blood samples 22.22(5.63) per 1000 BN cells. One year later (2001) the incidence of micronuclei in pregnant woman slightly decreased and reached the value of 26.98(4.50), while in cord blood it slightly increased up to 26.58(6.85) per 1000 BN cells. CONCLUSION: The monitoring data obtained in this study have shown significantly increase of micronuclei (2- to 3-fold) in study groups in 2000 and 2001.


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