New forms of diagnosis and treatment of cow´s milk allergy

Cow`s milk is one of the first components introduced into the diet, and it is the most common cause of food allergy in children younger than 5 years, affecting about 2% to 3% of infants and young children in developed countries. Furthermore, cow`s milk allergy represents a heavy burden for patients, particularly for infants and their families because accidental ingestion can lead to severe systemic reactions and in the worst case to death. The project is dedicated to the molecular and immunological characterization of cow`s milk allergens, the evaluation of their allergenic activity and clinical relevance and the determination of IgE- and T-cell epitopes. Recombinant cow`s milk allergens and epitopes thereof will be used to generate new diagnostic tests based on microarrayed allergens and epitopes for the assessment of antibody responses (IgE, IgG, IgA, IgM) in clinically well characterized cow`s milk allergic patients. Based on the identification of the most important cow`s milk allergens and their IgE- and T-cell epitopes, hypoallergenic allergen-derivatives will be engineered and characterized which can be used for safe and effective immunotherapy of cow`s milk allergy.

Cows milk is one of the first components introduced into the diet, and it is the most common cause of food allergy in children younger than 5 years, affecting about 2% to 3% of infants and young children in developed countries. Furthermore, cows milk allergy represents a heavy burden for patients, particularly for infants and their families because accidental ingestion can lead to severe systemic reactions and in the worst case to death. The project was dedicated to the molecular and immunological characterization of cows milk allergens, the evaluation of their allergenic activity and clinical relevance and the determination of IgE- and T cell epitopes. Recombinant cows milk allergens were produced in E. coli, purified and spotted onto microarrays. With this tool it is now possible to test patients more efficiently and establish individual antibody profiles. In collaboration with Swedish researchers a Swedish birth cohort was investigated in more detail. The IgG antibody profiles against the recombinant and natural milk allergens and against more than 100 other food, respiratory and insect proteins were measured in pregnant women. By measuring the protein-specific IgG levels in human milk, cord blood and the new-borns it was possible to trace the transfer of IgG from mothers to their infants. Moreover we could observe the establishment of an IgG immune response in infants. Another part of my project dealt with the characterization of hydrolyzed formulas that are available for avoidance of allergic reactions in cows milk allergic children and for prevention of allergy development in high risk infants. Using biochemical techniques and antibody probes highly specific for seven different cows milk allergens, a blinded analysis of a panel of eight cows milk formulas, one non-hydrolyzed, two partially hydrolyzed, four extensively hydrolyzed and one amino acid formula, was conducted. The investigated CM formulas showed a great variability regarding the presence of immunogenic CM components, IgE reactivity, allergenic activity and induction of pro-inflammatory cytokines. The results of our study showed that certain CM formulas without allergenic and low pro-inflammatory properties can be identified.