Modified th2 responses at high-dose exposures to allergen - Using an occupational model

Rationale: The relationships between allergen exposures and allergy and asthma are complex. High exposure levels to cat allergen are associated with IgG- and IgG(4)-specific antibody responses without sensitization or risk of asthma, a process described as a "modified Th2 response." Attenuation of risk of allergy and asthma at high exposure levels has been reported in longitudinal studies of both childhood and occupational asthma. Objectives:To investigate, using an occupational model, the relationships among estimated exposure to aeroallergens, the production of specific IgE, IgG and IgG(4) antibodies, and the prevalence of associated symptoms. Methods: Cross-sectional survey of employees exposed to rats at work on six pharmaceutical sites across the United Kingdom. A total of 689 (89%) provided a blood sample and completed a questionnaire. Measurements and Main Results: At highest exposure to rats, there was an attenuation of the exposure response for sensitization and symptoms. In contrast, the frequency of individuals producing high quantities of specific IgG and IgG4 increased with exposure intensity. Ratios of IgG(4)/IgE were highest in those handling the greatest number of rats. Risk of developing work-related chest symptoms was lower for those who produced both specific IgE and IgG4 Compared to those with specific IgE only. Conclusions: High exposure to rats is associated with lower rates of specific IgE and symptoms but an increased frequency of high specific IgG and IgG(4) production. Specific IgG, produced together with specific IgE may reduce the risk of developing work-related chest symptoms compared with when specific IgE is produced alone.