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

Abstract

Background: The role of natural aeroallergen exposure in modulating allergen-specific immune responses is not well understood.

Objective: We sought to examine relationships between mouse allergen exposure and mouse-specific immune responses.

Methods: 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.

Results: 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).

Conclusion: 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.

Figure 1

Boxplots of long-term variability of mouse allergen exposure (expressed as the log10 (standard deviation of log10 exposure) by job category. Each box plot indicates the minimum, 25th percentile, median 75th percentile, and the maximum of the data.

Figure 2

Plots depicting relationships between (a) level of exposure and (b) and long-term variability of exposure and +SPT. The relationships predicted by the statistical models are indicated by solid lines and 95% confidence intervals are indicated by dotted lines.

Figure 3

Plots depicting relationships between (a) level of exposure and (b) long-term variability of exposure and mouse-specific IgG₄. The relationships predicted by the statistical models are indicated by solid lines and 95% confidence intervals are indicated by dotted lines. Long-term variability is expressed as the log10 (standard deviation of exposure).

Figure 4

Surface plots depicting relationships between level of exposure, variability of exposure and risk of (a) +SPT and (b) mouse-specific IgG₄. Long-term variability is expressed as the log10 (standard deviation of exposure).

Figure 4

Surface plots depicting relationships between level of exposure, variability of exposure and risk of (a) +SPT and (b) mouse-specific IgG₄. Long-term variability is expressed as the log10 (standard deviation of exposure).