How is igg transported across placenta

These mothers were given injections of anti-D IgG at 28 weeks gestation. There appeared to be no difference in maternal levels of IgG at birth, but there were significantly lower transfer ratios of IgG2 but not of any other subclass. This suggests that the administered IgG could compete with transfer of endogenous IgG2, but a much larger cohort of rhesus negative pregnancies is required to study this further.

There may be a benefit to ensuring a time interval between maternal vaccination and anti-D infusion, if IgG2 is important for protection, and maternal vaccination studies should include Rhesus status in their analyses. Non-white women had higher levels of IgG2 and IgG3, but the transfer ratios were lower in these pregnancies and thus cord levels were not significantly different.

Older mothers had lower total IgG levels, but there was no effect on transfer nor cord levels. Interestingly, women who had previously had a live birth had higher levels of total IgG and IgG1 at birth. However, this was not reflected in neonatal blood, and the transfer ratio between maternal and cord blood was reduced in these pregnancies.

Thus, as previously discussed, although maternal and cord IgG levels are positively correlated, the ability of the placenta to transfer IgG may be limited by potential saturation of Fc transport receptors at higher IgG concentrations.

Previous studies found no effect of parity on the transfer of antigen-specific IgG in placental malaria nor HIV infection 36 , 38 , nor on cord blood antigen-specific antibody concentrations The only other subclass transfer study relating to malaria and hypergammaglobulinemia also reported no effect of parity Finally, we investigated the impact of maternal vaccination on levels and transfer of IgG subclasses. Tdap vaccination status had no impact on maternal nor cord IgG concentrations.

However, there was a positive correlation between later gestation at Tdap vaccination and higher transfer ratios of all four subclasses.

For example, a study by Eberhardt et al. Perhaps more intriguing is our observation that babies born to influenza vaccinated mothers have significantly higher levels of IgG4. Vaccinated mothers also have higher IgG4 levels, which is interesting given that pregnancy has been previously associated with an elevated IgG4 response to seasonal influenza vaccine We have previously shown that timing of influenza vaccination impacts on anti-influenza levels in babies, with the highest levels if mothers were vaccinated 4—24 weeks before delivery 42 , but here we find no effect of influenza vaccine timing on neonatal levels nor transfer of the IgG subclasses.

In summary, the current study provides a detailed analysis and update on the transplacental transfer of IgG subclasses, including a review of 17 previous studies investigating maternal to fetal transfer of IgG subclasses.

Most studies agree that IgG1 is the most efficiently transferred antibody subclass, with lower transfer of IgG2—4. We conclude that transfer of the IgG2—4 subclasses varies widely between study populations, but that IgG2 transfer may not be as poor as often stated. The diverse findings between studies could be due to differences in ethnicity, parity, vaccination status including gestation of vaccination , gestation at delivery even within term delivery populations and birth centiles between study populations; clinical parameters that were associated with transfer ratios of total IgG and IgG subclasses from mother to fetus in our study.

It is important that we continue to offer maternal vaccination to all women. Encouragingly, neonatal levels of total IgG and IgG subclasses seems largely unaffected by maternal factors. However, administration of anti-D may result in lower IgG2 levels in the neonate, and maternal flu vaccination may result in higher levels of IgG4. Therefore, the impact of both of these interventions on the neonatal immune response should continue to be explored.

The studies involving human participants were reviewed and approved by London-Hampstead and Yorkshire and the Humber Research Ethics Committees. Written informed consent to participate in this study was provided by all participants. BD and SB contributed to patient recruitment and collection of clinical data. TC, TR, and MB processed the samples, carried out the laboratory investigations, and contributed to data preparation.

GV performed the statistical analysis and contributed to figure and table preparation. BK and CJ contributed to study design and execution. BH conceived and designed the overall study and drafted the manuscript. All authors contributed to the drafting and revision of the manuscript. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research, or the Department of Health.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. We thank Anna Bosanquet and Marielle Bouqueau for their work in consenting women and their babies and Safiyah Ismail for her work optimizing the FcRn western blot.

We also thank all the families who took part in this study by donating blood and placentas to research. Supplemental Figure 1. Correlation between timing of maternal blood draw and maternal concentrations of total IgG and IgG subclasses profiles.

Concentration of total IgG and IgG subclasses in women plotted against the timing of their blood draw. Supplemental Table 1. Descriptive statistics of maternal to fetal transfer of total IgG and IgG subclasses.

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