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Published ahead of print on April 7, 2006, doi:10.1164/rccm.200506-964OC

Am. J. Respir. Crit. Care Med., Volume 174, Number 1, July 2006, 21-25

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Submitted on June 22, 2005
Accepted on April 6, 2006

Modified TH2 Responses at High Dose Exposures to Allergen; Using an Occupational Model

Hayley Jeal1, Adrian Draper2, Jessica Harris1, Anthony Newman Taylor1, Paul Cullinan1, and Meinir Jones1*

1 Department of Occupational and Environmental Medicine, NHLI, Imperial College, London, United Kingdom, 2 Department of Respiratory and General Medicine, St. George's Hospital, London, United Kingdom

* To whom correspondence should be addressed. E-mail: meinir.jones{at}imperial.ac.uk.

Rationale: The relationships between allergen exposures, allergy and asthma are complex. High exposure levels to cat allergen are associated with IgG and IgG4 specific antibody responses without sensitisation 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 between 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 UK. 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 sensitisation 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 to when specific IgE is produced alone.
Key words: IgG, IgG4, laboratory animal allergy, occupational allergy, exposure




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