Dose effects of respiratory neoantigen exposure on primary allergic sensitization

Abstract

Background Respiratory allergen dose effects on the human immune response are incompletely understood. We prospectively examined the effect of respiratory antigen dose exposure on the rate of primary allergic sensitization to a neoantigen, keyhole limpet hemocyanin, using a unique model of human nasal allergic sensitization. Methods Fifty-one atopic human volunteers were consecutively assigned to 1 of 4 groups completing a 4-week nasal sensitization protocol. Group protocols varied only in initial antigen dose exposure. Intranasal doses of 0.1, 10, 1000, or 100,000 μg keyhole limpet hemocyanin with adjuvant intranasal diesel exhaust particles were administered in the research laboratory. Antigen-specific IgE, IgG, and IgG4 were measured in nasal lavage samples at completion of the protocol. Results Allergic sensitization rates for the 0.1, 10, 1000, and 100,000 μg dose groups were 0%, 100%, 57%, and 11% respectively (p= 0.0003). Mean IgE levels for the 10 μg, 1000 μg, and 100,000 μg doses were 29.2, 11.5, and 1.2 U/ml, respectively (Kruskal-Wallis test, overall p= 0.001; 10 μg vs. 1000 μg p= 0.05; 1000 μg vs. 100,000 μg p= 0.034). All subjects produced antigen-specific IgG. Conclusions Respiratory antigen dose at the time of first exposure influences the mucosal immune response in antigen naïve humans. The risk of primary allergic sensitization may paradoxically be decreased by initial high levels of respiratory antigen exposure through the induction of a modified, non-allergic immune response. Clinical Pharmacology & Therapeutics (2005) 77, P3–P3; doi: 10.1016/j.clpt.2004.11.013