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Modified Th2 Responses at High-Dose Exposures to Allergen

Using an Occupational Model

Department of Occupational and Environmental Medicine, Imperial College (NHLI); and St. George's Hospital, London, United Kingdom

Correspondence and requests for reprints should be addressed to Meinir Jones, Ph.D., Department of Occupational and Environmental Medicine, Faculty of Medicine, Imperial College (NHLI), 1B Manresa Road, London SW3 6LR, United Kingdom. E-mail: meinir.jones{at}imperial.ac.uk

Rationale: The relationships between allergen exposures and allergy and asthma are complex. High exposure levels to cat allergen are associated with IgG- and IgG₄-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 IgG₄ 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 IgG₄/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 IgG₄ production. Specific IgG₄ produced together with specific IgE may reduce the risk of developing work-related chest symptoms compared with when specific IgE is produced alone.

Key Words: IgG • IgG₄ • IgE • laboratory animal allergy • occupational allergy

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