Diagnostic procedures of offending food in food allergy include clinical history, skin testing, in vitro specific IgE tests, and elimination and provocation tests. Oral provocation test is the most relevant method for determination of causative food. Especially, double-blind placebo-controlled food challenge currently remains the _??_old standard·for the diagnosis of food allergy. This method is, however, occasionally followed by severe adverse reactions such as anaphylaxis. Skin testing such as prick or scratch tests is relatively safely done as compared to oral challenge test. However, this method is affected by medication such as anti-histamines and anti-allergic drugs as well as oral challenge test. In vitro specific IgE tests are safely performed without effects by medications, but occasionally show false positive or false negative results as well as skin tests. These tests indicate the presence of allergen-specific IgE, but they do not establish the diagnosis of clinical food allergy.
A recent study by Sampson et al demonstrated 95% positive predictive value of specific IgE to egg, milk, peanut and fish using CAP system (Pharmacia & Upjohn), in which upper limits of range of measurement is extended. A patient with a serum food allergen-specific IgE titers in excess of the 95% predictive value may be considered reactive, and an oral food challenge would not be warranted. We also determined the 95% positive predictive value of specific IgE titers to egg white and ovomucoid in egg allergy. The 95% positive predictive values are 10.5Ua/ml of egg white and 6.22Ua/ml of ovomucoid for freeze-dried egg white with allergenicity close to raw egg. For diagnosis of heated egg, 62.1Ua/ml of egg-white-specific IgE titers and 19.6Ua/ml of ovomucoid-specific IgE titers were 95% positive predictive values. The measurement of IgE to ovomucoid, of which IgE-binding activity is relatively stable to heat treatment, was superior to egg white in diagnosis of clinical hypersensitivity to heat-treated egg white.
Next, we measured IgE-binding activity to pepsin-treated ovomucoid by RAST inhibition in order to distinguish challenge-negative and -positive subjects with high egg-white-specific IgE titers. The IgE from challenge-negative subjects showed lower activity to bind to pepsin-resistant IgE epitope(s). Furthermore, the egg-allergic children from which IgE antibodies bind weakly to pepsin-stable epitope(s) on ovomucoid is likely to outgrow as compared to subjects with IgE reactive to pepsin-stable epitopes on ovomucoid. The reason is why the children with IgE recognizing pepsin-resistant epitope(s) retain hypersensitive reactions to egg white ingestion in spite of development of pepsin secretion with age.
Domain 3 of ovomucoid contains pepsin-stable IgE-epitope(s). Measurement of specific IgE to domain 3 was useful not only to diagnosis the clinical hypersensitivity after egg ingestion but also to predict the outcome of egg allergy in subjects with high IgE titers for egg white.
Development of hypoallergenic foods is promising area in treatment of food allergy. Because these products contribute to improvement of QOL of food-allergic patients and their family. Several hypoallergenic products of cow milk and rice have been already available. We have developed heated and ovomucoid-depleted egg white and proved it hypoallergenic by double-blind and placebo-controlled food challenge. Approximately 97% of the subjects hypersensitive to heated egg white showed negative reactions to this sample.
Many investigators are working on novel form of immunotherapy for food allergy. In future, food products inducing tolerance will be developed. We extensively digested ovomucoid with pepsin to an extent of elimination of IgE-binding capacity and assessed its cytokine-producing activity from peripheral blood mononuclear cells from eggallergic subjects. IFN-γ production by the ovomucoid fragments was unchanged and IL-4 production
View full abstract