Both the variability and level of mouse allergen exposure influence the phenotype of the immune response in workers at a mouse facility

Abstract

The role of natural aeroallergen exposure in modulating allergen-specific immune responses is not well understood. We sought to examine relationships between mouse allergen exposure and mouse-specific immune responses. New employees (n = 179) at a mouse facility underwent repeated assessment of mouse allergen exposure, skin prick tests (SPTs), and measurement of mouse-specific IgG levels. Relationships between the mean level of exposure, variability of exposure (calculated as log deviation), and time to development of immunologic outcomes were examined by using Cox proportional hazards models. By 24 months, 32 (23%) participants had experienced a positive SPT response, and 10 (8%) had mouse-specific IgG₄. The incidence of a positive SPT response increased as levels of exposure increased from low to moderate, peaking at 1.2 ng/m³, and decreased beyond this point (P = .04). The more variable the exposure was across visits, the lower the incidence of a positive SPT response (hazard ratio [HR], 0.17; 95% CI, 0.07-0.41). Variability of exposure was an independent predictor of a positive SPT response in a model that included both exposure metrics. In contrast, the incidence of mouse-specific IgG₄ increased with increasing levels of mouse allergen exposure (HR, 2.9; 95% CI, 1.4-6.0), and there was evidence of a higher risk of mouse-specific IgG₄ with greater variability of exposure (HR, 6.3; 95% CI, 0.4-95.2). Both the level and variability of mouse allergen exposure influence the humoral immune response, with specific patterns of exposure associated with specific immunophenotypes. Exposure variability might be a more important predictor of a positive SPT response, whereas the average exposure level might be a more important predictor of mouse-specific IgG₄.