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

Abstract

Primary allergic sensitization—IgE formation after Ag exposure—is fundamental in the development of allergic respiratory disease. With the rising prevalence of asthma and allergic rhinitis, improved understanding of the determining factors for allergic sensitization is needed. Human epidemiologic studies suggest high-dose allergen exposure may paradoxically protect against sensitization. Prospective human studies of allergen dose effect on primary allergic sensitization are lacking. We prospectively examined the effect of respiratory Ag dose exposure on the rate of primary allergic sensitization to a neoantigen, keyhole limpet hemocyanin, using a unique model of human nasal allergic sensitization. Atopic human subjects were exposed to 0.1-, 10-, 1,000-, or 100,000-μg doses of intranasal keyhole limpet hemocyanin in conjunction with adjuvant intranasal diesel exhaust particles. Ag-specific IgE, IgG, and IgG4 were measured in nasal lavage samples at the conclusion of the sensitization protocol. Allergic sensitization rates for the 0.1-, 10-, 1,000-, and 100,000-μg dose groups were 0, 100, 57, and 11%, respectively. All subjects produced Ag-specific IgG with the highest levels observed in the high-dose group. These results provide direct evidence that primary allergic sensitization may be prevented by initial high levels of respiratory Ag exposure through induction of a modified, nonallergic immune response. This Ag dose effect was capable of overcoming the well-established allergic adjuvant effects of diesel exhaust particle exposure. Whether this immune response represents durable allergic tolerance is not yet known. Studies investigating the molecular mechanisms of this non-IgE response may be useful in developing therapy to prevent allergic sensitization.

Nasal Responses in Asthmatic and Nonasthmatic Subjects Following Exposure to Diesel Exhaust Particles

“…It should be noted that exposure to a higher dose (i.e., 1 mg DEP) did not induce an increased IgE response (Diaz-Sanchez et al, 1994), which could be due to inherent toxicity and/or paradoxical protection due to a high allergen dose (Riedl et al, 2005). Because DEPs are composed with dissimilar physicochemical properties, the possibility exists that responses (related to immune and inflammatory changes) may be qualitatively or quantitatively different, depending on which properties are involved in the response.…”

Neonatal exposure with LPS and/or allergen prevents experimental allergic airways disease: Development of tolerance using environmental antigens

“…7 Our data support the hypothesis that airways allergy, both asthma and allergic rhinitis, results from failure to tolerize actively the airway mucosal immune system early in life through antigen stimulation. 26,31,32 If the early response is not appropriately directed, subsequent mucosal contact with innocuous aeroallergens results in allergic sensitization.…”

Impact of Urbanization on the Proteome of Birch Pollen and Its Chemotactic Activity on Human Granulocytes

“…Traffic emissions such as diesel exhaust particles have an impact on the immune system and promote a Th2-dominated immune response [7]. Furthermore, it was shown that diesel exhaust particles can prime the immune system to develop a neoantigen proallergenic immune response with high levels of allergen-specific IgE [8, 9]. …”