R. Urbanek

Prenatal allergen contact with milk proteins

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.

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

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.

Latex sensitization in spina bifida appears disease-associated.

OBJECTIVE The high prevalence of latex sensitization (up to 80%) in patients with spina bifida (SB) has been attributed to repeated exposure to latex products, whereas disease-associated factors have not been considered. METHODS We compared children with SB (n = 21) and children with posthemorrhagic or congenital hydrocephalus (PH, n = 32), all of whom had a ventriculoperitoneal shunt since young age. Latex sensitization, number of operations, atopic history, and total IgE levels were evaluated. RESULTS The following characteristics were recorded: age (SB: 52 months, range 1 to 264 months; PH: 71 months, range 1 to 192 months) and mean number of operations (SB: 2. 09; PH: 2.53). Of the SB group, 43% (9 of 21) showed elevated latex-specific IgE antibodies in contrast to 6% (2 of 32) in the PH group (P <.01). Latex-specific IgE antibodies were detected by 1 year of age, and one surgical operation was sufficient to induce latex-specific IgE-antibody production in patients with SB. CONCLUSIONS The results suggest that the SB population bears a disease-associated propensity for latex sensitization. Sensitization to latex antigens may occur after the very first contact, arguing for latex avoidance measures from the very beginning of life.

Maternally delivered nutritive allergens in cord blood and in placental tissue of term and preterm neonates

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.

IgE-mediated allergic reaction to hyaluronidase in paediatric oncological patients

Abstract Hyaluronidase has been gaining increasing interest as a spreading factor for better penetration of chemotherapeutics into CNS tumours. Five out of 16 patients with CNS tumours treated with hyaluronidase in addition to chemotherapeutic agents developed symptoms of immediate type allergic reactions, therefore we sought to characterize the harmful allergenic proteins of the bovine testes hyaluronidase enzyme preparation (Neopermease). The role of specific IgE for the allergic reaction was investigated. Using an immunoblotting technique, we investigated sera from 16 children treated with Neopermease (5 of them having developed anaphylactic reactions), 5 patients with atopy (atopic eczema) with high total IgE levels and 4 healthy children. SDS-PAGE of hyaluronidase preparation Neopermease revealed two major bands at 73 and 41–43 kDa. In all 5 sera from patients with adverse reactions, binding of specific IgE antibodies to the 73 and 41–43 kDa bands was found. Two patients reacted with the 73 kDa band exclusively, two patients reacted with both bands, one patient displayed IgE only to the 41–43 kDa band. A specific inhibition of IgE-binding to both bands was achieved after preincubation of the sera in four out of five patients with partially purified bovine hyaluronidase. Furthermore preincubation with gelatin, a stabilising agent in the commercial extract, led to a partial inhibition in the sera of three patients. No specific IgE binding was detected either in the sera of atopic patients, or in the control group. Conclusion IgE mediated allergic reactions to hyaluronidase may occur in paediatric oncological patients treated with hyaluronidase. Whether these children are sensitized by intravenous hyaluronidase treatment or by cross-reactivity of other preformed IgE antibodies, yet to be specified, remains to be elucidated.

Cow's milk‐specific cellular and humoral immune responses and atopy skin symptoms in infants from atopic families fed a partially (pHF) or extensively (eHF) hydrolyzed infant formula

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 cows 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).

Detection of IgE Antibodies Specific for Allergens in Cow Milk and Cow Dander

Sera from patients with cow milk protein allergy (n = 6) and cow dander allergy (n = 5) were analyzed for reactivity of IgE antibodies specific for allergens derived from milk and cow dander. The cow milk- and cow dander-allergic patients exhibited elevated specific IgE levels to milk and to cow dander, respectively, as determined by RAST. IgE immunoblot analysis revealed that cow milk-allergic patients exhibited IgE binding to the milk allergens casein, beta-lactoglobulin, alpha-lactalbumin and bovine serum albumin. Four of six cow milk-reactive patients also exhibited IgE binding to cow dander proteins with molecular weights of 20, 22, 36, 50 and > 200 kD. IgE from the sera of cow dander-allergic patients reacted with the major allergens of cow dander (20 and 22 kD) and with other proteins with molecular weights of 24, 36, 42, 50 and 70 kD. Only one out of five of these sera displayed IgE reactivity with cow milk proteins with molecular weights of 69, 92 and > 200 kD. Inhibition studies revealed the cross-reactive nature of the IgE antibodies. Preincubation of cow milk-positive sera with cow milk and subsequent immunoblotting led to complete blocking of IgE binding to cow dander proteins and to cow milk proteins. Preincubation of cow milk-positive sera with cow dander extract led to blocking of IgE binding only to defined cow milk proteins: these could be identified in 2 cases as casein and in 1 case as beta-lactoglobulin.(ABSTRACT TRUNCATED AT 250 WORDS)

Characterization of antigens and allergens in hypo-allergenic infant formulae.

The antigenicity and allergenicity of so-called hypo-allergenic infant formulae is mainly determined by the degree of hydrolysis and ultrafiltration. Five different formulae were investigated by means of immunoblotting and RAST in order to characterize the antigens and allergens regarding their molecular weights, molecular origin and their ability to bind human IgG and IgE antibodies: A non hydrolysed infant formula (I-F), a mixture of the major cows milk proteins (PM), a whey-based infant formula (W-H), a whey-based and ultra-filtrated infant formula (U-H), a casein/whey-based infant formula (CW-H). By immunoblotting we demonstrated that all tested formulae still contain antigens with molecular weights from 3 to 67 kD. But when compared with I-F and PM the antigen content of the hydrolysed formulae was considerably lower. The lowest antigen content could be demonstrated in U-H, which contains casein fragments (3–6 kD) and beta-lactoglobulin and its fragments (6–18 kD). W-H and CW-H contain bovine serum albumin, beta-lactoglobulin, casein and their fragments (3–67 kD). All hydrolysed formulae tested showed a reduced IgE-binding capacity. Three out of 12 cows milk allergic children possessed IgE binding to U-H or W-H, and 5 of them IgE against CW-H.ConclusionThe enzymatic hydrolysis plus ultra-filtration seems to be the most efficient method to reduce the antigen content of so-called hypo-allergenic infant formuale.

Early Sensitization to Airborne Allergens

We report the case of a 7-month-old child with failure to thrive. Celiac disease was suspected because of highly raised antigliadin IgA and IgG antibodies and subtotal villous atrophy. In peripheral blood mononuclear-cells cellular proliferation was found in response to birch pollen, rye pollen and hazelnut extract. Born in June 1992 the infant had not yet experienced a birch pollen season. He had been fed with birch pollen allergy-associated carrot, apple and potato beginning at 6 weeks of life. In the serum, specific IgG, IgM and IgA to birch pollen and profilin, rye pollen and hazelnut antigens were detectable, indicating possible in utero sensitization or T cell cross-reactivity due to early sensitization with related food antigens.

Glucocorticoids enhance interleukin-4 production to neo-antigen (hyaluronidase) in children immunocompromised with cytostatic drugs

Immunoglobulin E (IgE)‐mediated immediate‐type allergic reactions to hyaluronidase have been observed in children with central nervous system (CNS) tumors. Glucocorticoids, used as therapy for brain edema, are discussed controversially as T helper 2 (Th2) stimulatory factors. In this study we investigated the role of glucocorticoids on a Th2 cytokine‐promoting effect in children with CNS tumors. Peripheral blood mononuclear cells (PBMCs) from: 29 children suffering from malignant brain tumors, of whom 23 received short‐term glucocorticoid treatment (for 3–4 days) during the course of chemotherapy; 18 children with nephrotic syndrome or renal transplantation receiving long‐term glucocorticoid treatment; and 13 healthy children, were incubated with phytohemagglutinin (PHA) and/or anti‐CD28 monoclonal antibody (mAb) and, in a second approach, with hyaluronidase. The concentrations of Th cell‐mediated cytokines – interleukin (IL)‐4, IL‐10, and interferon‐γ (IFN‐γ) – were measured in supernatants. The IL‐4 production of PBMCs incubated with PHA/anti‐CD28 mAb from children with repeated co‐administration of glucocorticoids, hyaluronidase, and cytostatic drugs (median: 249.9 pg/ml; range: 234.4–261.7) was significantly higher (p < 0.0001) than IL‐4 production of PBMC from children of all the other groups (median: 86.18; range: 16.0–212.5). There was no significant difference in the levels of IL‐10 and IFN‐γ within the groups. PBMCs stimulated only with hyaluronidase failed to produce detectable levels of cytokines. The results of this study indicate that repeated co‐administration of glucocorticoids and hyaluronidase (a neo‐antigen) enhance IL‐4 production in vitro and thus may induce the production of specific IgE antibodies in children immunocompromised with cytostatic drugs. Hyaluronidase itself does not stimulate in vitro IL‐4 synthesis in PBMCs of children receiving cytostatic drugs.