Why igg can cross placenta

GPnotebook no longer supports Internet Explorer. To ensure the site functions as intended, please upgrade your browser. Microsoft is encouraging users to upgrade to its more modern Edge browser for improved security and functionality. This site is intended for healthcare professionals. In this study, we evaluated concentrations and transplacental transfer ratios of the IgG subclasses in a healthy UK-based cohort of mother-cord pairs, and investigated associations with maternal, obstetric, and fetal factors.

In agreement with previous studies, we found a strong association between maternal and cord IgG for all subclasses. Levels of IgG subclasses were the same between venous and arterial blood samples from the umbilical cord, but there was a significantly higher level of total IgG in arterial blood. We found no correlation between placental FcRn protein levels and IgG transfer in our cohort, suggesting that IgG is the main determinant of observed differences in transplacental transfer ratios at term.

Neonatal IgG1 and IgG4 levels were increased with later gestation at delivery, independent of any increase in transplacental transfer, indicating that the benefit of later gestation is through accumulation of these subclasses in the fetus. Neonatal IgG2 levels and transfer ratios were reduced in rhesus-negative pregnancies, suggesting that administered anti-D antibodies may compete for transplacental transfer of this subclass.

Maternal influenza vaccination resulted in elevated maternal and neonatal levels of IgG4, whereas maternal Tdap vaccination had no impact on neonatal levels of the subclasses, nor transfer.

However, within Tdap vaccinated pregnancies, later gestation at Tdap vaccination was associated with higher transplacental transfer. Our study provides information regarding levels and transfer of IgG subclasses in healthy term pregnancies and demonstrates the importance of recording detailed clinical information in studies of antibody transfer, including parity, ethnicity, and timing of maternal vaccine delivery. The neonatal period is a high-risk period for infectious diseases. Neonates are afforded some protection through passive immunity provided by maternal immunoglobulin IgG actively transferred across the placenta during pregnancy.

This phenomenon has enabled maternal vaccination strategies aimed at boosting fetal levels of antigen-specific IgG for diseases associated with high neonatal mortality and morbidity. Maternal administration of tetanus and pertussis vaccines have both been highly successful at reducing rates of neonatal disease 1 — 4. Transfer of IgG across the placental barrier is thought to involve interaction between IgG and the neonatal Fc receptor FcRn in the placental syncytiotrophoblast 5.

For FcRn to bind IgG, IgG must therefore be taken up from the maternal circulation by the syncytiotrophoblast into endosomes which undergo acidification. The endosomes then fuse with the fetal side of the syncytiotrophoblast, leading to an increase in the pH, and the release of IgG into the stroma 8.

It is not currently known how IgG crosses the stroma and the second placental barrier—the fetal endothelium—but FcRn may also be present in this endothelial layer 9.

Other receptors or Fc-binding proteins found in the placenta could also be involved 6. More detail on the process of IgG transfer is available in our recently published review on FcRn-mediated transplacental antibody transfer IgG is divided into four subclasses, which cross the placenta with differential efficiency.

The issue of transplacental transfer of the IgG subclasses is important, as they play diverse roles in immunity, and their production is differentially induced by distinct pathogens and vaccines [reviewed in 11 ]. These usually reference one review 12 that has a graph illustrating data from a single study We have identified 17 papers that have measured maternal and cord levels of the four IgG subclasses 13 — 29 Figure 1. Calculating the mean from these papers produces transfer ratios of 1.

The reasons for these varying reports could be due to many differences in study populations including ethnicity, parity, BMI, placental weight, birth weight, gestation at birth, as well as maternal antigen exposure through vaccination or infection modifying antibody phenotype including subclasses, antigen-specificity, and glycosylation.

Figure 1. Overview of studies investigating maternal to fetal transfer ratios of IgG subclasses. We identified 17 papers that measured paired maternal and cord levels of all four IgG subclasses 13 — 22 , 24 — The line graph represents the mean to fetal transfer ratio on a log 2 axis.

The dotted black line indicates the mean of the 16 studies. For Malek et al. For two studies, we performed ratio calculations based on reported maternal and cord concentrations 21 , For two other studies, values were calculated by reading from the published graphs 13 , For Costa-Carvalho et al. In Hay et al.

Many previous studies of placental antibody transfer have been relatively small and often have not interrogated the effect of clinical variables other than gestation at delivery.

Later gestation at delivery is associated with an increase in maternal to cord transfer ratios and in concentrations of antibody in cord blood 11 , 30 — However, several additional maternal and fetal factors have the potential to impact on placental antibody subclass transfer. This includes fetal sex, Rhesus status and associated anti-D antibody administration , maternal vaccination, BMI, parity and ethnicity, among others.

It is important to understand the role of these factors when performing maternal vaccination studies in diverse patient populations. We performed IgG subclass analysis on a large number of maternal and cord blood samples, including an assessment of the impact of maternal and fetal factors on IgG subclass levels and transplacental transfer.

Serum samples were obtained from corresponding maternal and—cord blood pairs, as part of two maternal vaccination studies. Healthy women with singleton pregnancies with no known complications nor chronic or acute diseases were recruited. Detailed clinical data including BMI, parity, age, ethnicity, gestation at delivery, infant sex, birth weight, and maternal vaccination status were recorded.

Serum samples were obtained from mothers near the time of birth between 1 day before delivery and 3 days after delivery , and from the umbilical cord vein or artery within 1 h of delivery.

Where possible, blood was collected separately from both the umbilical vein and the umbilical artery and this was recorded. Blood was collected into serum-separating tubes BD and left to clot for a minimum of 15 min before spinning at G for 10 min.

This kit utilizes a high affinity protein stain which is compatible with subsequent western blotting. Following staining, membranes were imaged on the ImageQuant camera system LAS ; GE Healthcare to enable normalization of subsequent specific protein bands. This approach for normalization was employed due to the high variability of common protein loading controls in the placenta Bound antibody was detected through incubation with 0.

FcRn levels relative to total protein was determined by densitometry ImageJ. Statistical analyses were performed in GraphPad Prism v8. IgG concentrations were log transformed natural Log prior to analysis to achieve normality. Maternal to fetal transfer ratios were calculated by dividing the IgG concentration in cord blood, by the IgG concentration in paired maternal blood. These ratios were then log 2 transformed prior to analysis.

Unadjusted and adjusted effects were estimated by simple and multiple linear regression models in Stata v Clinical characteristics of the study subjects are shown in Table 1. There was no significant effect of timing of maternal bleed and maternal IgG concentrations Supplemental Figure 1. The maternal to fetal transfer ratio of IgG1 1. IgG3 also exhibited a small, but significantly higher transfer ratio 1. When transfer ratios were normalized to total IgG levels in mothers, as a measure of relative transfer efficiency, a similar pattern of transfer was observed, although IgG3 was no longer significantly higher than IgG4 Figure 2C.

Paired comparison revealed significantly higher levels of total IgG and IgG1, and significantly lower levels of IgG2 and IgG4 in cord blood serum compared to matched maternal serum Figure 2E. IgG3 was not significantly different between mothers and infants. Correlation plots of maternal and cord IgG levels show a positive correlation between maternal and cord antibody for total IgG and all IgG subclasses.

Within the subclasses, the strongest correlation between maternal and cord levels is for IgG4, with the weakest correlation for IgG2 Figure 2F. Additional descriptive statistics on the transfer of the subclasses is provided in Supplemental Table 1.

Figure 2. Maternal and cord blood IgG subclass profiles and transfer ratios. IgG4 breaking the rules. Immunology : 9. Losen M. Anti-inflammatory activity of human IgG4 antibodies by dynamic Fab arm exchange.

Science : Van Ree R. Perdok G. Van Doorn H. Tan K. Normal human immunoglobulin G4 is bispecific: it has two different antigen-combining sites.

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It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide. Sign In or Create an Account. Sign In. Advanced Search. Search Menu. Article Navigation. Close mobile search navigation Article Navigation. Volume Article Contents Abstract. Human placenta: relative content of antibodies of different classes and subclasses IgG1—IgG4 containing lambda- and kappa-light chains and chimeric lambda-kappa-immunoglobulins.

Lekchnov , Evgenii A. Oxford Academic. Sergey E. Pavel S. Valentina N. Georgy A. Cite Cite Evgenii A. Select Format Select format. Permissions Icon Permissions. Abstract The specific organ placenta is much more than a filter: it is an organ that protects, feeds and regulates the growth of the embryo. Open in new tab Download slide.

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