The impact of protein nitration on food allergy induction

As epidemiological data indicate a rising prevalence of allergic diseases, there is a growing need to identify risk factors for allergy induction. Recently, the nitration of pollen proteins e.g. by ambient pollutants was revealed to increase the allergic potential of inhalative allergens. However, nitration might not only occur by environmental pollution but also during inflammation and as a result of aging in the human body. Through nitration of tyrosine residues on self antigens the development of autoimmune reactions might be promoted by evasion of immunological self-tolerance. Additionally, also gastric inflammatory processes, such as Helicobacter pylori infections, could substantially modify proteins of the daily diet and alter the immunogenicity of these proteins with influence on food allergy induction. Since the 1980ies the association between gastric inflammations and food allergy induction has been repeatedly described in scientific literature. The enhancement of food specific IgE has been ascribed to different aspects, such as hereditary or alimentary factors, increased mucosal permeability and acid-suppression medication for treatment of dyspeptic disorders. Nevertheless, also protein nitration during inflammatory responses could directly influence protein allergenicity. In the current study we therefore aim to analyze the impact of protein nitration on food allergy induction via the oral route. The gastric digestion has been revealed to have an important gate-keeping function in food allergic reaction interfering with the stability of ingested proteins. Therefore, the question will be addressed whether digestion stability of food allergens might be modified by nitration of tyrosine residues. Additionally, the nitration capacity of Helicobacter pylori urease will be analyzed by in vitro experiments. Using our previously established murine food allergy model the impact of nitrated dietary compounds on the development of allergic responses will be determined. Based on the results generated from this project we expect to gain novel insights into risk factors for food allergy with eminent influence on current treatment protocols of gastric inflammatory diseases.

Previous studies have demonstrated that chemical modification of certain protein components can occur due to environmental pollution leading to the so-called protein nitration. This chemical protein modification, which was detected for pollen allergens in urban dust samples, was described to be associated with a higher allergenic potential of these pollen allergens.Besides the effect of pollutants on inhalative allergens, protein nitration has also been described in inflammatory environment and as a result of the ageing process or to be triggered by special dietary compounds in the human body. As the properties of the gastrointestinal tract play a define role in this process, the completed project aimed for analysing the influence of protein nitration on food components with special regards to the impact on food allergy.Our studies demonstrated that the influence of these chemical changes on major food allergens was depending on protein structure. For a part of the analysed food allergens protein nitration was revealed to induce an increased degradation of the allergen in the gastrointestinal tract, as well as a change of protein regions, which are crucial for the recognition by antibodies or immune cells. We have demonstrated for the nitrated model allergen Ovalbumin, an important egg allergen, a reduced capacity to trigger de novo food allergy in a murine model. However, in situations where IgE antibodies were already formed, mediators eliciting allergic symptoms were increasingly released. In further experiments we were able to confirm these first data and verified also for the major milk allergen ?-lactoglobulin an essential influence on protein characteristic by nitration. In an experimental food allergy model we have demonstrated that the nitrated milk allergen has an enhanced potential to trigger a severe allergic (anaphylactic) response compared with the untreated milk protein.Our data indicate that depending on specific characteristics of food compounds, protein nitration is associated with an enhanced risk for severe allergic reactions in already existing food allergies, which has substantial impact on the safety of food allergic patients.