Two types of IgE-mediated food allergy can be distinguished: primary and secondary food allergy. The latter is the result of initial sensitization via non-gastrointestinal routes, e.g. the lung or skin, and subsequent cross-reactivity of allergen-specific IgE antibodies (Ab) with structural related proteins in particular foods. The aim of this thesis was to investigate such cross-reactive Ab in birch pollen-related food allergy, a highly prevalent secondary food allergy in Austria, and in delayed hypersensitivity to red meat, which has recently been reported in the United States.
More than 70% of birch pollen-allergic individuals develop IgE Ab specific for the major birch pollen allergen Bet v 1 that cross-react with the structurally related apple allergen Mal d 1. Detection of allergen-specific IgE Ab is one important step in allergy diagnosis. Since the use of apple extracts bears several limitations for allergy diagnosis because they may lack intact Mal d 1 we investigated whether recombinant (r) Mal d 1 can improve this situation. We found that rMal d 1 enhances the sensitivity of detection of specific serum IgE. Furthermore, rMal d 1 increased the sensitivity of skin prick tests of apple-allergic individuals. Thus, in addition to in vitro diagnosis, one single isoform of recombinant Mal d 1 is a useful tool for in vivo diagnosis.
Only recently, patients suffering from delayed type meat allergy have been reported who develop systemic reactions several hours after ingestion of red meat and display increased levels of IgE specific for the carbohydrate Galalpha1-3Galbeta1-4GlcNAc-R (alpha-gal). Tick bites have been considered to be responsible for primary sensitization to alpha-gal via the skin. We investigated 20 Austrian patients who experienced such reactions and characterized their alpha-gal-specific IgE and IgG responses in more detail.
Bovine gamma globulin (BGG) was the protein in meat extract most frequently recognized by their IgE-Ab. Both IgE- and IgG-binding to BGG were completely abolished after pre-incubation with alpha-gal. This finding indicated that BGG-specific Ab selectively recognized the carbohydrate epitope without involvement of amino acid residues. IgG to alpha-gal are highly abundant natural Ab in humans. However, neither the depletion of autologous alpha-gal-specific IgG Ab nor the addition of alpha-gal-specific IgG Ab from non-allergic individuals changed the IgE-recognition of BGG of meat-allergic patients. Specific IgG-response in meat-allergic patients to alpha-gal was dominated by IgG1 and IgG3 Ab, whereas in patients with birch pollen-related apple allergy IgG4 Ab dominate the specific IgG-response to Mal d 1. In summary, we found that in patients with delayed meat-allergy the enhanced alpha-gal-specific IgE levels are accompanied by high levels of alpha-gal-specific IgG1 devoid of IgE-blocking activity. This subclass distribution is different from the subclass distribution in birch pollen-related food allergy and also distinct from natural alpha-gal-IgG responses in non-allergic individuals.