Regulation of IgE antibody production by serum molecules. V. Evidence that coincidental sensitization and imbalance in the normal damping mechanism results in "allergic breakthrough".

Experiments presented in this paper were designed to test a new concept concerning the possible pathogenesis of the allergic phenotype. This concept, termed "allergic breakthrough" considers that one of the avenues toward the allergic phenotype involves coincidental sensitization combined with an imbalance in the normal damping mechanism that serves to limit IgE antibody production. The three predictions of this concept that can be tested experimentally are: 1) manipulations that are effective in heightening or re-establishing the damping mechanism should manifest persistence insofar as IgE antibody synthesis to the relevant allergen is concerned; 2) once allergic breakthrough has occurred, the height of production of IgE antibodies specific for the sensitizing agent should remain elevated at levels characteristic of the allergic phenotype, even after the threshold of damping activity has returned to a normal level; and 3) allergic breakthrough should display specificity in that breakthrough would occur in response to subsequent exposure to the specific antigen to which coincidental sensitization initially occurred, but not for other unrelated antigens. The studies presented herein confirm each one of these predictions, thereby providing substantial support for the validity of this concept as one possible distinguishing feature between individuals manifesting the nonallergic and allergic phenotypes, respectively.