Materno–fetal passage of nutritive and inhalant allergens across placentas of term and pre‐term deliveries perfused in vitro

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Abstract
The pre- and postnatal environment appears to be of crucial importance for the manifestation of allergic diseases, which often begin during infancy. Although T cell reactivity of fetal origin to a range of common allergens is present in most cord blood samples, the immunological basis remains unclear. In order to test the hypothesis of transplacental allergen transfer we studied double-sided open ex vivo perfusion experiments of isolated placental cotyledons with the nutritive allergens beta-lactoglobulin (BLG) and ovalbumin (OVA) and the inhalant major birch pollen allergen Bet v1. Placentas of full-term and pre-term newborns were obtained immediately after delivery to recover functionally active maternal and fetal circulations. Thus, a fetal artery and a fetal vein were cannulated and perfused with pure medium (fetoplacental circulation), whereas the intervillous space of placentas was flushed with allergen containing medium by puncture of the basal plate (maternoplacental circulation). Samples that were collected throughout the perfusion experiment from fetal venous outflow were tested by allergen-specific enzyme-linked immunosorbent assays (ELISA) for the presence of allergens indicative of materno-fetal transplacental passage. We observed transplacental transfer of BLG, OVA and Bet v1 in placentas of term as well as premature deliveries. The respective allergen was readily detectable in fetal effluent at the beginning of the perfusion experiment and allergen levels reached a plateau after about 2 h. The steady state transfer rate of BLG and OVA in term placentas was 0.012% +/- 0.001 and 0.013% +/- 0.001 of total dose, i.e. 130.21 +/- 7.41 ng/mL and 115.83 +/- 6.07 ng/mL, respectively. The observed transfer rate of Bet v1 after 2h of perfusion was 0.155% +/- 0.034 of total dose, that is 2.41 +/- 1.36 ng/mL. Transplacentally transferred concentration of BLG and OVA in pre-term placentas increased continuously throughout perfusion time from 5.32 +/- 0.92 ng/mL at 1 min to 87.53 +/- 21.93 ng/mL at 120 min and 1.35 +/- 0.31 ng/mL at 1 min to 112.87 +/- 5.25 ng/mL at 150 min, respectively. Allergen-specific cord blood reactivity may be attributed to low levels of allergens crossing the human placenta and providing the fetus with the necessary stimulus for T cell priming.

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