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Updated: Jun 13, 2025
A Murine Model of Fetal Exposure to Maternal Inflammation to Study the Effects of Acute Chorioamnionitis on Newborn Intestinal Development
Published on: June 24, 2020
Transamniotic Fetal Immunotherapy with Secretory IgA: A Potential Novel Ancillary Strategy for the Prevention of
Ashlyn E Whitlock1, Kamila Moskowitzova1, Ina Kycia1
1Department of Surgery, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Introduction:
Secretory immunoglobulin-A (SIgA), which is not produced perinatally, binds bacteria enhancing mucosal immunity. Higher levels of intestinal bacteria bound by SIgA are protective against necrotizing enterocolitis. Transamniotic fetal immunotherapy (TRAFIT) has previously been used to deliver SIgA to the fetal digestive tract, however, with unclear functional impact. We sought to determine whether SIgA administered via TRAFIT could functionally bind intestinal bacteria postnatally.
Methods:
Fetuses (n = 38) from 4 dams underwent intra-amniotic injections of human SIgA on gestational day 19 (E19; term = E22-E23). After spontaneous delivery, pups were survived for 1-2 days postnatally before intestinal contents were procured and submitted to flow cytometry. Specimens were stained for bacteria (Syto-GFP) and human SIgA (PE) to prevent cross-reactivity with maternal rat SIgA.
Results:
Overall survival was 94.7% (36/38). SIgA-bacterial complexes were identified in all samples at all time points showing significantly higher positive PE events than unstained controls (p = 0.03-0.05). The proportion of bacteria bound by IgA decreased daily, from 45.6% to 29.9% bound at 4-6 days post-TRAFIT, respectively (overall p = 0.05).
Conclusions:
TRAFIT with secretory IgA leads to functionally IgA-bound bacteria into the postnatal period and may be a novel strategy for enhancing early mucosal immunity, potentially protecting the neonate against necrotizing enterocolitis.
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