Evidence of an affinity threshold for IgE-allergen binding in the percutaneous skin test reaction

Background: Atopy is an aberrant immune response involving allergen-specific IgE production, though serum IgE concentration is not an entirely reliable diagnostic tool, particularly for epidemiological and genetic studies. There is no clear correlation between IgE and other indicators of atopy such as skin prick tests SPT)s, and physiological associations are difficult to justify in cases with detectable IgE but negative SPT results. Objective: IgE reflects the number of molecules available to produce an atopic response, but the degree of the response is determined by the binding strength affinity) between receptor-bound IgE and the allergen. We sought to determine if there was an association between binding affinity and SPT results in people with histories of atopy. Methods: Standard SPTs whole allergen extracts) were administered to people with histories of sensitivities to ragweed and house dust mite. The concentrations and affinities of serum allergenspecific IgEs were determined using the purified allergens Amb a 1 and Der p 1. Results: There was a positive correlation between weal area and allergen-specific IgE among SPT-positive donors. However, for those individuals with detectable amounts of allergen-specific IgE, there was considerable overlap of IgE values between SPT-positive and -negative groups. Among sensitized donors, IgE-allergen interactions were characterized by two or three specific reactions of very high affinity K_A range 10⁸-10¹¹ M). Negative SPT reactions were associated with lowered IgE binding affinities to major allergens. This delimited two groups with atopic disorders: specific IgE⁺)/SPT⁺) and specific IgE⁺)/SPT^-). Conclusion: The product of antibody affinity and concentration, which we define as antibody capacity CAP = K_A × IgE), is more informative with regard to describing allergen sensitivity than antibody concentration alone. Antibody binding capacity provides physiological evidence of atopy in some subjects who do not test positively by common methods and suggests an affinity threshold to produce a positive SPT reaction.