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Notes: 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.

Notes: Background There is growing evidence that the development of allergic sensitization can be influenced by environmental co-factors. Studies showed that growing up on a farm can protect children against allergic sensitization. However, little is known whether this ‘farming effect’ can only be observed in early lifetime or whether it also plays a role in later childhood.Objective The aim of our study was to test whether a farming environment is negatively associated with a new occurrence of skin prick test (SPT) positivity in school children. As a secondary outcome we investigated whether children living on a farm lose their allergic sensitization more frequently than other children.Methods In a longitudinal design, 1150 elementary school children (mean age 7.8 years, SD 0.7) were recruited from nine different areas of Austria in 1994. A questionnaire and an SPT involving seven common aero-allergens were performed at study entry and at follow-up 3 years later.Results A total of 844 children, who underwent two SPTs, were included in the analyses; 15.1% of their families reported working on a farm. Adjusting for potential confounders (parental education, number of siblings, sex, family history of allergy), parental farming was inversely related to the prevalence and new occurrence of SPT positivity [no farming 12.2%, part-time farming 6%, full-time farming 2.2% incidence; odds ratio (OR) farming vs. non-farming 0.34, 95% confidence interval (CI) 0.12–0.98]. Furthermore, children living in a farming environment were more likely to lose their SPT positivity during follow-up (no farming 14.6%, part-time farming 50%, full-time farming 60% loss of sensitization; OR farming vs. non-farming 8.06; 95% CI 2.05–31.75). No difference in the pattern of sensitization to specific allergens could be observed between farming and non-farming children.Conclusion A farming environment has a strong negative effect on the development of allergic sensitization. Furthermore, the study provides evidence that atopic children living on a farm lose their SPT positivity more frequently than children from non-farming environments.

Notes: 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.

Notes: Eosinophil cationic protein (ECP) and eosinophil protein X (EPX) are well established as markers of eosinophil activation. We analyzed ECP and EPX concentrations in nasal lavage fluids (NALF) of 378 neonates during their first 4 weeks of life. Inclusion criteria were a positive history of parental allergy and a positive skin prick test or specific IgE (RAST class ≥2) against at least one out of a panel of common aeroallergens in one or both parents. Twenty-four infants with no history of parental allergy were used as controls. A volume of 2 ml of 0.9% saline was instilled into each nostril and immediately recovered by a suction device. ECP and EPX were analyzed by radioimmunoassay. In 65 samples of three consecutive lavages, EPX was detected in nine samples (13.8%) in the control group, whereas it was detected in 197/360 samples (54.7%) in the study population. The corresponding figures for ECP were 17/65 (26.2%) in the control group and 173/365 (47.4%) in the study group. Both proteins showed a skewed distribution (median/5–95th percentiles for ECP: 0 µg/l [0–69.4] and EPX: 6.6 µg/l [0–73.2]). The differences between the control group and the study group were statistically significant, regardless of the allergic disease of the parents. In children of allergic parents, activation proteins of the eosinophil granulocyte are released on the nasal mucosal surface in about 50% of the studied population at the age of 4 weeks. This early onset of eosinophil activation in the nasal respiratory epithelium may reflect a genetic predisposition to allergy or early exposure to allergens.

Notes: Background:  Type-I-allergy to natural rubber latex (NRL) has been shown to be more prevalent among certain groups of patients. Children suffering from chronic renal failure (CRF) could be a suspected risk group because of their intense exposure to latex through catheters, gloves and anesthetic equipment during frequent hospitalizations from early life on. We investigated the prevalence of latex-sensitization among this group of patients and sought to identify risk factors.Methods:  Ninety-three patients (mean age 10.5 years) suffering from CRF were assessed by questionnaire-based history (details on renal disease, number and kind of surgical procedures, family and personal history of atopic diseases, allergic reactions to NRL, and the use of pacifiers) and by measurement of total and latex-specific serum immunoglobulin (Ig)E.Results:  Ten of 93 (10.8%) patients showed elevated latex-specific IgE-levels. One of 10 patients reported clinical symptoms to latex-allergen, but no allergic reactions to NRL during medical care were reported. Sensitized patients were significantly more likely to be atopic, reflected by a positive history of other allergies as well as elevated total serum IgE-levels, and had a significantly higher number of urogenital surgeries (P = 0.02 in all cases, Fisher's exact and Wilcoxon test, respectively).Conclusion:  This study demonstrates that children with CRF are at increased risk of latex-hypersensitivity. Significant associations with atopy and repeated surgeries were observed. Larger studies are required to elucidate whether these children are also at increased risk of anaphylaxis and therefore deserve preventive measures.

Notes: Background: Hydrolyzed milk formulas are recommended to feed infants at high risk of atopy if breast-feeding is not possible. We studied the specific cellular and humoral immune response to cow's milk proteins and occurrence of atopic dermatitis under different feeding regimens: two hydrolyzed infant milk formulas (partially [pHF] and extensively hydrolyzed [eHF]) and under exclusive breast-feeding (BF). Methods: Seventy-two infants from families with atopic symptoms were randomized in the pHF and eHF groups, respectively. At 6 and 12 months of age, peripheral blood mononuclear cell proliferation along with specific IgG and IgE to cow's milk proteins was determined in infants fed pHF or eHF, respectively, and those who had not yet received any formula at 6 months of age (BF). Cases of atopic dermatitis were recorded throughout the first 12 months of life, and their severity was evaluated with SCORAD points. Results: A significantly decreased proliferation to cow's milk caseins was found in the pHF group compared to the exclusively breast-fed group. Medians of stimulation indexes for CAS at 6 months were as follows: pHF 1.18; n=24; BF 1.70; n=24 (P=0.033, Mann-Whitney U-test). Higher levels of plasma IgG antibodies to BCAS were found in infants fed pHF than in those fed eHF at 12 months. Optical density (OD): (25th percentile; median; 75th percentile): pHF: 0.00; 0.14; 0.38; n=30; eHF: 0.00; 0.03; 0.14; n=28; P=0,089, Mann-Whitney U-test. Cow's milk-specific IgE was detected at 6 months as follows: BF: 3 of 24; eHF: 2 of 21; pHF: 0 of 23. The number of cases of atopic dermatitis and their severity did not differ among the groups during the first 12 months. Conclusions: Feeding pHF appears to suppress cow's milk-specific cellular responses and stimulate specific IgG production. Specific IgE sensitization can occur also with breast-feeding.