Initial High-Dose Nasal Allergen Exposure Prevents Allergic Sensitization to a Neoantigen

Abstract

Purpose of the Study. Epidemiologic studies have suggested that high-dose allergen exposure may protect against primary allergic sensitization—the formation of immunoglobulin E (IgE) after initial antigen exposure. This study uses a human nasal allergic sensitization model to evaluate the effect of the dose of the antigen on the rate of primary sensitization to a neoantigen, keyhole limpet hemocyanin (KLH). Study Population. Fifty-one healthy nonsmoking atopic subjects aged 18 to 55 years. Atopic status was defined by a positive skin-prick test to at least one aeroallergen; the subjects therefore had a propensity to mount an allergic (IgE) response to respiratory antigen exposure. Methods. Subjects underwent a 33-day sensitization protocol including initial exposure to 0.1-, 10-, 1000-, or 100 000-μg doses of intranasal KLH as well as later exposure to adjuvant intranasal diesel exhaust particles. At the conclusion of protocol, antigen-specific IgE, IgG, and IgG4 were measured in nasal lavage samples. Results. The rates of allergic sensitization, defined as detectable KLH-specific IgE, for the 0.1-, 10-, 1000-, or 100 000-μg dose groups were 0, 100, 57, and 11%, respectively. Furthermore, the mean KLH-specific IgE levels decreased with increasing doses of initial antigen exposure. Antigen-specific IgG and IgG4 were produced by all subjects, with the highest levels observed in the high-dose group. Conclusions. Initial high levels of respiratory antigen exposure may prevent primary allergic sensitization through induction of an antigen-specific non-IgE humoral immune response. Reviewer Comments. In children at high risk of allergic sensitization, a means of preventing primary sensitization and inducing durable allergic tolerance would be of great value. This study found that initial high-dose exposure to a neoantigen, KLH, results in a humoral immune response with high levels of antigen-specific IgG, including IgG4, and low levels of KLH-specific IgE. Whether these findings apply to other respiratory antigens remains unclear. The mechanism underlying this induction of tolerance remains unclear, and it is also not known whether this immune response represents durable allergic tolerance. Future studies investigating these issues are needed to move toward potential primary prevention therapy for allergic disease.