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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: Allergic reactions to Hymenoptera stings are frequently observed all over Europe. Rarely they may induce long-standing morbidity or even be fatal. Several investigations have shown that the emergency treatment given to these patients is often inadequate. Cutaneous symptoms respond well to antihistamines and also to adrenaline. Adrenaline is the mainstay for outside hospital treatment of more severe reactions involving the respiratory tract (bronchial asthma, laryngeal oedema) and the cardiovascular system (anaphylactic shock). Inhaled adrenaline is especially useful in respiratory symptoms, while parenteral application of adrenaline is prefered for shock treatment. All patients with severe respiratory or cardiovascular reactions must be hospitalized, treated under intensive care conditions and observed for at least 24 hr. Emergency medications including adrenaline for inhalation or for self-injection must be given to all patients with a history of systemic allergic reactions to hymenoptera stings. These patients must also get instructions for safety measures to avoid further stings. They should be referred to an allergist in order to evaluate the indication for venom immunotherapy.

Notes: To investigate the year-to-year variation of mite antigen density (Der p I, Der f1) in dust from mattresses and the relevance of residential factors for antigen load, information derived from an epidemiologic study including two surveys carried out in the households of a cohort of elementary school children (n= 1291) was analysed.When considering residences with measurements taken in both years in question (n= 1050), rank-correlation indicated a predominance of stability for both antigens (Der p I: rs= 0-82, p=0.0001; Der f I: rs=0.72, P= 0.0001), Using multiple regression analyses, significant associations between antigen concentrations and a variety of residential factors were found. Use of a blanket of animal hair, use of a cover or underblanket, wet spots in the bedroom, higher relative humidity and a low storey level were significantly associated with increased concentrations of Der p I, whereas inverse relationships between this antigen and room temperature, number of persons per m2 as well as use of underfloor heating were seen. Regarding Der f I, older mattresses, use of a cover or underblanket, higher weight of sampled dust, high educational level and higher ratio of inhabitants per m2 were significantly associated with increased concentrations of the antigen. On the other hand, lower Der f I concentrations were found when interior sprung mattresses were used and when the mattress was ‘treated regularly’.In conclusion, two measurements, 1 year apart from each other, show that stability of mite antigen concentrations predominated. Our data suggest that allergic patients should be advised against living in lower storeys and damp homes and to use a newer or encased mattress and to give preference to a residence with underfloor heating.

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: Twenty patients with a proven sensitization to grass pollens were treated with parenteral “priming” and subsequently with either oral “booster” (n-10) or placebo (n=10) extension course. The study was carried out in a double-blind manner. Cumulative preseasonal parenteral dosage was 3,100 NU (Noon Units), patients in the oral group subsequently received 123.9 mg of grass pollen extract during the pollen season. No side effects were noted after intake of the oral preparation. No significant differences (95% confidence interval) were noted comparing results of in vivo (skin prick test and conjunctival provocation test) and in vivo tests (specific serum IgE- And IgG-antibodies) between the two groups. Analysis of symptom and medication scores as well as subjective assessment of patients revealed no superiority of oral “booster” over placebo. Data obtained in this study does not support the concept of combined parenteral and oral treatment. This is in contrast to work reported previously.

Notes: Immunotherapy with Hymenoptera venoms is widely used throughout the world and is accepted as an effective treatment for most patients with Hymenoptera venom allergy. There are, however, still some unresolved problems with this form of treatment. At present there is no definite test which makes it possible to identify patients at risk - and thus candidates for immunotherapy - unequivocally. On the basis of prospective studies on the natural history of Hymenoptera allergy, venom immunotherapy is indicated in adults with severe systemic anaphylaxis. It is usually not necessary in patients with large local reactions only. Children with mild systemic reactions, e.g. urticaria, will need immunotherapy only in case of repeated reactions and/or a high risk of re-exposure. The selection of venoms for immunotherapy may lead to some confusion owing to common antigenic determinants shared by venoms of various Hymenoptera species. Many different regimens for immunotherapy have been proposed. At present, the three main are: rush, stepwise or clustered and classical. The maintenance dose of 100 μg usually protects from life-threatening reactions. However, in some patients 200 μg are necessary for complete protection. The usual interval between maintenance injections is 4 to 6 weeks. In many patients a strong increase of venom specific serum IgG-antibodies usually parallels clinical protection induced by venom immunotherapy, although many exceptions have been reported. Allergic side effects of venom immunotherapy are not rare, especially with honey bee venom and during the initial phase of dose increase. The question of the duration of venom immunotherapy is handled differently: although some authors recommend treatment for life, most suggest treating patients until skin tests and RAST become negative.

Notes: In general, specific immunotherapy with hymenoptera venoms can be considered as safe, but occasionally there are patients who cannot reach the maintenance dose due to repeated systemic reactions (RSR) or who suffer from RSR during maintenance therapy. In a multicenter retrospective study comprising seven departments in Germany, Austria and Switzerland 23 patients with RSR were reported from approximately 3000 patients treated with hymenoptera venoms (bee and wasp venom to approximately equivalent frequency). From these, 22 were allergic to bee venom and only one to vespid venom. In general the clinical symptoms of RSR were milder than the initial reaction. But 4/23 (18%) exhibited cardiovascular reactions up to full shock. Neither anamnestic details, reactivity in skin tests or in vitro tests revealed a special pattern of patients with RSR. In some patients, however, an extremely high reactivity in the skin test was found and may indicate the possibility of further RSR.

Notes: We investigated the effect of rush and long-term venom immunotherapy on histamine release parameters in bee venom allergic patients. Ten patients received rush venom immunotherapy, and histamine release data were obtained immediately before and after treatment. 17 patients were assessed by histamine release 24 to 63 months after termination of long-term venom immunotherapy. A control group of 10 non-allergic subjects was included in this study. Histamine released from whole blood was determined in a sensitive radio-enzymatic assay using a single isotope technique. Bee venom phospholipase A-induced histamine release from whole blood proved to be a test procedure of high specificity and sensitivity. Eight of 10 untreated patients and no control subject showed significant antigen-induced histamine release. Results obtained from patients immediately after successful rush venom immunotherapy showed an important decrease (mean 45.9%) of total histamine content of basophil leukocytes in all patients. Antigen-induced maximum histamine release was found to be increased in one, decreased in two and unchanged in seven patients. In patients who received long-term immunotherapy cell sensitivity to phosopholipase A was significantly lower than in a group of untreated patients (P≤ 0.002). These results suggest that even years after discontinuation of immunotherapy, histamine release parameters reflect patients' protection from systemic sting reactions as assessed by sting challenges. Histamine depletion of basophils induced by rush immunotherapy may play an important role in patients' protection immediately after termination of the rush regimen.

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.