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Routing Kinetics of Human Immunoglobulin G after Transamniotic Fetal Immunotherapy (TRAFIT) in a Rodent Model
Ashlyn E. Whitlock, MD, Daniel F. Labuz, MD, Ina Kycia, PhD, David Zurakowski, PhD, Dario O. Fauza, MD, PhD
Department of Surgery, Boston Children’s Hospital and Harvard Medical School Boston, MA
Background:
Immunoglobulin-G (IgG) has successfully been administered to the fetus via transamniotic delivery, however by unknown pathways. We sought to determine the route of fetal IgG kinetics after exogenous intra-amniotic injection.
Methods:
Fetuses (n=78) from Sprague-Dawley dams (n=6) received intra-amniotic injections of 15mg/mL solution of human-IgG on gestational-day 18 (E18; term=21-22 days). Samples of amniotic-fluid, amnion, chorion, placenta, fetal serum, liver, and stomach-aspirate were procured on E19 (n=23), E20 (n=26), and E21 (n=29) for quantification of human-IgG by ELISA. Statistical analysis was by median regression with Bonferroni-adjusted p<0.017.
Results:
Survival was 86% (67/78). Human-IgG was detected in all sites across all time points, although at significantly higher levels in the gestational membranes and fetal serum than in the stomach aspirate (p<0.001), and liver (p<0.001). Gestational membranes showed a daily decrease after injection, stabilizing by E20 and E21 (figure; p=0.792 to <0.001). Placental levels were significantly lower at E21 than E19 (p=0.010). Stomach aspirate and amniotic fluid levels trended in parallel to each other. At term, the fetal serum showed the highest human IgG levels of all fetal sites.
Conclusions:
The chronology of exogenous IgG kinetics after intra-amniotic injection is suggestive of gestational membrane uptake followed by placental transport, combined with, but independent of, fetal ingestion. This is compatible with IgG transport driven by FcRN receptors, which are located in both placental endothelium and gastrointestinal epithelium.
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