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Notizen: Background 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.Objective 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.Methods 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.Results 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 2 h 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.Conclusion 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.

Notizen: Background Cellular proliferation to various allergens (Dermatophagoides pleronyssinus, β-lactoglobulin, bovine serum albumin, ovalbumin) has been found in cord blood cells. Whether this reflects a sensitization during foetal life is uncertain.Objective We studied the cellular reactivity and cytokine production of cord blood cells in response to cow's milk proteins in a randomely selected group of newborns. The delineation of possible in utero allergen contact was attempted.Objective Cord blood mononuclear cells from 39 neonates were incubated with cow's milk proteins (α-lactalbumin, β-lactoglobulin, casein, α-casein, β-casein, k-casein, bovine serum albumin) for 7 days, and proliferation was assessed by incorporation of [3H]thymidine. Cord blood cell-derived interferon-γ (IFNγ) and interleukin-4 (IL-4) secretion was evaluated in response to allergen or phytohaemagglutinin (PHA) stimulation.Results A pronounced proliferation of cells stimulated with α-lactalbumin (ALA; mean stimulation index 8.0, 95% confidence interval 5.2–10.8), β-lactoglobulin (BLG; mean stimulation index 5.9, 95% confidence interval 3.2–8.6) and α-casein (2.6, 95% confidence interval 2.9–9.1), as opposed to unstimulated cells in medium, was found. No correlation was found between cellular proliferation to milk proteins and parental atopy, maternal total IgE or cord blood IgE. IFNγ production (but not IL-4) was inducible by PHA (range 429–1810 pg/ml), but only in one individual upon stimulation with BLG. Preferentially, reduced IFNγ levels were found in individuals with positive parental allergic history.Conclusion The recognition of allergen by cord blood cells indicates that allergen priming must occur prenatally. The relevance for subsequent sensitization is unclear.

Notizen: Background The proliferation of cord blood mononulear cells in response to nutritive and inhalant allergens implies intrauterine exposure with resulting T cell priming. However, the mechanisms triggering these fetal allergen-specific immune responses are incompletely understood.Methods We studied the placental release of endogenous β-lactoglobulin (BLG) and ovalbumin (OVA) by the use of an open ex vivo placental perfusion model. Preterm and term placentas were obtained immediately after delivery to recover functionally active fetal and maternal circulations. Fetal and maternal perfusate samples were collected throughout the perfusion experiments with medium. Matched cord blood samples were collected separately. All samples were tested for the presence of OVA and BLG by allergen-specific ELISAs.Results In 16 out of 19 placentas, the nutritive allergens could be detected both in fetal and maternal perfusate samples. Fetal wash out levels of the allergens BLG and OVA from the placental tissue of preterm and term deliveries were observed in traces and up to 44.4 and 2.6 ng/mL, respectively. In cord blood of preterm and term neonates, BLG and OVA could be detected at concentrations up to 16.7 and 5 ng/mL, respectively.Conclusion These findings provide direct evidence for the release of tiny amounts of nutritive allergens from placental tissue indicating diaplacental allergen transfer and fetal exposure to nutritive allergens in vivo.