Birgit Ahrens

Impact of in utero Th2 immunity on T cell deviation and subsequent immediate-type hypersensitivity in the neonate.

It was the aim of this study to analyze the impact of maternal Th2 immune responses on onset and subsequent development of allergen‐specific immunity and immediate‐type hypersensitivity in early childhood. In a well characterized mouse model of Th2 immunity, BALBu2009/u2009c mice were sensitized to ovalbumin (OVA) before mating followed by allergen aerosol exposure during pregnancy. At the end of pregnancy mice developed allergen‐specific Th2u2009/u2009Th0 immunity and immediate‐type hypersensitivity responses to OVA. T cells from these newborns, when restimulated with PMAu2009/u2009ionomycin, demonstrated a lowered capacity to produce IFN‐γ. To assess whether prenatal allergen exposure favors postnatal onset of a Th2‐type immune response, these offspring were immunized to a novel antigen by a single injection of β‐lactoglobulin (BLG). In contrast to offspring from non‐sensitized mothers, offspring from OVA‐sensitized mice showed both higher anti‐BLG immunoglobulin titers and higher frequencies of immediate‐type skin test responses. Our data suggest that Th2u2009/u2009Th0 immunity present during pregnancy has a decisive impact on shaping of the Th1u2009/u2009Th2 T cell profile in the neonate. Furthermore, this effect favors the development of Th2 immune responses, when mice are exposed to a novel antigen during early childhood.

Allergic sensitization and allergen exposure during pregnancy favor the development of atopy in the neonate.

Background: Several studies have considered that the in utero environment plays an important role in the onset of the allergic phenotype. We assessed whether allergic sensitization and allergen exposure during pregnancy favor the postnatal onset of allergy in the neonate. Methods: BALB/c mice were sensitized to ovalbumin (OVA) before mating followed by allergen aerosol exposure during pregnancy. T and B cell responses in offspring were followed up until day 60 postpartum. At the age of 4 weeks offspring were exposed to a heterologous antigen, β-lactoglobulin (BLG). Results: Pregnant mice developed immediate hypersensitivity responses and Th-2/ Th-0 immunity following allergen aerosol exposure. At birth, T cells from offspring of nonsensitized BALB/c mice were characterized by an impaired IFN-γ production, which was lowered even further in offspring of OVA-sensitized BALB/c mice. Offspring of OVA-sensitized BALB/c mice responded with immediate-type cutaneous hypersensitivity reactions to OVA which could be related to the pre- and postnatal transfer of maternal OVA-specific IgG1 antibodies. After exposure to BLG, offspring of OVA-sensitized BALB/c mice developed an accelerated Th-2-driven immune response compared to offspring from nonsensitized BALB/c mice as indicated by enhanced anti-BLG IgG1 antibody production and increased numbers of positive immediate-type cutaneous hypersensitivity reactions to BLG. Conclusion: Our data suggest that Th-2/Th-0 immunity present during pregnancy has a decisive impact on shaping the Th-1/Th-2 T cell profile in response to postnatal allergen exposure.

Life-Threatening Vallecular Cyst in a 3-month-old Infant: Case Report and Literature Review

Laryngeal cysts represent an inhomogeneous collection of benign laryngeal abnormalities.1,2 Several classifications are reported according to their histologic structures, their size, their contents, or their localization within the larynx. Etiology and pathogenesis are still not fully understood, and a variety of terms for the same histopathologic subject cause confusion. The vallecular cyst for instance has been named in the literature as mucus retention cyst, epiglottic cyst, baseof-the-tongue cyst, and ductal cyst.3 In this case a laryngeal cyst localized in the vallecular space of a 3-month-old infant is reported. The lesion led to a life-threatening event during anesthesia. Case Report

Oral administration of bacterial lysates attenuates experimental food allergy.

Background: Modulating early immune response by application of bacteria and their by-products has been suggested as a preventive strategy against the development of allergic diseases. In light of this, the aim of the study was to test the effects of oral administration of bacterial lysates (BL) in a rat model of food allergy. Methods: BL or PBS were administered orally to neonatal Brown Norway rats up to an age of 42 days. Additionally, animals were sensitized 3 times (days 35, 40 and 45) intraperitoneally with ovalbumin (OVA). On days 60 and 61, rats were locally challenged with OVA by gavage feeding. Results: Detection of increased allergen-specific Ig serum levels and proliferative responses of spleen mononuclear cells confirmed systemic sensitization. In serum of animals that received BL in addition to OVA sensitization, the levels of allergen-specific IgE and IgG were significantly reduced compared to animals which were not exposed to BL. Allergen-stimulated lymphocytes from spleen and mesenteric lymph nodes of BL-treated animals showed a significantly elevated cytokine production of IL-10. To assess local functional changes of the intestinal barrier we measured the intestinal permeability, which was increased in OVA-sensitized and challenged animals compared to nonsensitized controls, yet significantly reduced in sensitized animals which received BL. Conclusion: These data suggest that local administration of BL (pathogen-associated molecular patterns) in the intestine exhibits immuno-modulating effects. Furthermore, pathophysiological features of food allergy, such as the loss of gut mucosal integrity, might be reduced by the treatment with BL.

Development of an animal model to evaluate the allergenicity of food allergens.

Scope: Considering the increasing numbers of patients suffering from food allergy (FA) as well as the great variety of novel foods and food compositions, an unmet need exists for the development of preclinical approaches to characterize the allergenic potential of proteins. The aim of our study was to evaluate the allergenicity of different food allergens in a rat model. Methods: Brown Norway rats were sensitized to protein extracts (RuBisCO, apple, soy, peanut, garden pea) or ovalbumin (OVA) combined with Bordetella pertussis and aluminium hydroxide, followed by oral allergen challenges. Results: Allergen-specific serum immunoglobulin production and the proliferation of mononuclear cells from spleen confirmed sensitization. To assess functional alterations in the gut, intestinal permeability was measured, which increased in sensitized and challenged animals compared to non-sensitized controls. Allergens with high allergenic potential (peanut, OVA, soy) caused a stronger immunological response than allergens with low allergenic potential, such as RuBisCO and apple. Moreover, the immunological responses were reduced when using boiled instead of raw soy and pea proteins. Conclusion: This model mimics key features of FA and facilitates investigating the allergenicity of allergens in novel food or food compositions in vivo.

Hydrolyzed Formula With Reduced Protein Content Supports Adequate Growth: A Randomized Controlled Non-Inferiority Trial

Objective: A high protein content of nonhydrolyzed infant formula exceeding metabolic requirements can induce rapid weight gain and obesity. Hydrolyzed formula with too low protein (LP) content may result in inadequate growth. The aim of this study was to investigate noninferiority of partial and extensively hydrolyzed formulas (pHF, eHF) with lower hydrolyzed protein content than conventionally, regularly used formulas, with or without synbiotics for normal growth of healthy term infants. Methods: In an European multi-center, parallel, prospective, controlled, double-blind trial, 402 formula-fed infants were randomly assigned to four groups: LP-formulas (1.9u200ag protein/100u200akcal) as pHF with or without synbiotics, LP-eHF formula with synbiotics, or regular protein eHF (2.3u200ag protein/100u200akcal). One hundred and one breast-fed infants served as observational reference group. As primary endpoint, noninferiority of daily weight gain during the first 4 months of life was investigated comparing the LP-group to a regular protein eHF group. Results: A comparison of daily weight gain in infants receiving LPpHF (2.15u200ag/day CI −0.18 to inf.) with infants receiving regular protein eHF showed noninferior weight gain (−3.5u200ag/day margin; per protocol [PP] population). Noninferiority was also confirmed for the other tested LP formulas. Likewise, analysis of metabolic parameters and plasma amino acid concentrations demonstrated a safe and balanced nutritional composition. Energetic efficiency for growth (weight) was slightly higher in LPeHF and synbiotics compared with LPpHF and synbiotics. Conclusions: All tested hydrolyzed LP formulas allowed normal weight gain without being inferior to regular protein eHF in the first 4 months of life. This trial was registered at clinicaltrials.gov, NCT01143233.