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 Division of Immunopathology
Department of Pathophysiology and Allergy Research
Center of Pathophysiology, Infectiology & Immunology

Medical University of Vienna

Vienna General Hospital, AKH, 3Q
Waehringer Guertel 18-20
A-1090 Vienna, Austria
 

Differential postnatal development of allergen-specific IgE-antibodies as early sign of atopy [Szepfalusi]

Project summary 2005 - 2006 

Allergic diseases such as allergic asthma and atopic dermatitis have multifactorial origins, arising from complex interactions between genes and environment. Early signs of allergy progress are the development of specific IgE antibodies (allergic sensitization), which mostly precedes or accompanies clinical symptoms in the first few months of life. As such, egg and milk sensitization have been shown to predict the subsequent development of allergic diseases. Recent findings clearly suggest, that those interventions with potential preventive effects on atopy/allergy development (such as growing up in a farming environment [1, 2], exposure to certain probiotics [3], hypoallergenic milk formulas [4] exhibit their single strongest effects if applied early in life, in particular before the age of 12 months, potentially also before birth.
Hypothesis: Defining the IgE-profile in the first few months of life helps to intervene earlier in an allergen-specific way.
This concept gains support by the subcutaneous immunotherapy trials in which early allergen-specific intervention could reduce new sensitizations in infants [5-7], thus demonstrating that allergen-specificity is important. We propose that by defining the IgE profile more precisely and by tracing the stability of this profile over time, it should be possible to intervene by using therapeutical vaccines earlier than currently recommendable. We further propose that the use of food proteins in such therapeutical vaccines should be considered and may lead to similar reduction of new sensitizations in infants, because food sensitization mostly precedes sensitization to aeroallergens.
Aim of the application: The focus of this application is to monitor the appearance of allergen-specific IgE antibodies in the peripheral blood of infants with and without positive family history of atopy. As the available blood volume is the limiting factor, microarray-chip technology will be applied. Prior to be used in the cohort study, this method will be validated for the relevant food allergen sources in infancy, which are represented by milk, egg, peanut, soy, fish, wheat, supplemented by cross-reactive proteins such as carrot, celery and apple. In an unselected, non-interventional cohort study, which is planned to start with the second year of the project, monthly blood sampling (by finger stick) and disease monitoring will be performed according to existing cohort protocols (Multicenter Allergy Study Group – MAS; SPACE - Study).
Methods: The challenge of this project is twofold. The detection of allergen-specific IgE antibodies by micro-arrayed allergen chips has been used reproducibly for aeroallergens and some pollen-allergy related food sources, but less experience is available for food proteins of relevance in infancy. We have established this technology to detect the presence and the relevance of allergen-specific IgE-antibodies (peanut, aeroallergens) in amniotic fluid, cord and maternal blood and blood from allergic children as compared to standard IgE measurements (CAP-system). Specifically, we will examine with defined sera from food allergic individuals (n=20; infants with egg, milk, wheat and peanut allergy, adults with peanut and cross reactive allergies such as birch-pollen-related oral allergy syndromes) whether reproducible results are achievable with very small serum sample volumes (40 μl). The ultimate volume is estimated to be 1-2 drops in order to be applicable in children for repeated measurements. The usefulness of whole blood versus serum will be validated as well. The methods for this validation process will encompass inhibition experiments, repeated measurements, use of validated sera from collaborative studies.
The second challenge of this project is the realization of a non-interventional cohort trial with extensive (monthly) blood samplings. To cope with this challenge, a multicenter trial will be initiated, and the basis of the success of this trial is repeated home visits by trained professionals, who will perform finger prick sampling sequentially on a monthly basis up to the 6th months, followed by the 9th and the 12th month of life. Standardized questionnaires will assess the development of clinical signs of allergic diseases. The analysis of these samples shall describe a) an age-related IgE reactivity profile, b) the change of individual IgE reactivity profiles over time, and c) the stability of the molecular IgE profile up to the age of 1 year.
Long term goal: The longterm goals are a) the description of the time-frame in which a stable allergen-specific IgE profile is set up, and b) the development of a preventive allergen-specific strategy to be implemented before/at this window of opportunity. These preventive approaches shall be designed on the basis of the expertise of SFB partners (Prof. Valenta, Prof. Niederberger, Prof. Wiedermann) using either tolerogenic molecules or native molecules combined with certain adjuvants.