Environmental and Occupational Disorders
HLA associations with occupational sensitization to rat lipocalin allergens: A model for other animal allergies?,☆☆

https://doi.org/10.1067/mai.2003.176Get rights and content

Abstract

Background: Laboratory animal allergy is a common occupational health problem affecting between 11% and 44% of exposed researchers. Allergy to rats and mice is most common, probably because these are the animals most frequently used. Objective: We hypothesized that HLA class II molecules, involved in the presentation of allergen to the T cell and likely candidates for controlling the immune response, might be associated with sensitization to rat urinary proteins among laboratory animal handlers. Methods: We undertook a cross-sectional study of 741 employees at 6 pharmaceutical sites across the United Kingdom who had contact at work with laboratory rats. In all, 109 cases with specific sensitization to rat proteins and 397 referents were HLA-typed for DRB1 and DQB1 loci. Amino acid analyses of significantly associated HLA molecules were carried out. Results: HLA-DR7 was associated with sensitization (odds ratio [OR], 1.82; CI, 1.12-2.97), respiratory symptoms at work (OR, 2.96; CI, 1.64-5.37) and, most strongly, sensitization with symptoms (OR, 3.81; CI, 1.90-7.65). HLA-DR3 was protective against sensitization (OR, 0.55; CI, 0.31-0.97). Amino acid analyses of these 2 molecules indicated a biologically plausible explanation for the associations. Conclusion: HLA phenotype is an important determinant of individual susceptibility to sensitization and asthma among laboratory animal workers. Similar mechanisms might apply in other animal allergies. (J Allergy Clin Immunol 2003;111:795-9.)

Section snippets

Methods

Between September 1999 and May 2001 we carried out cross-sectional surveys of employees at 6 pharmaceutical companies in the United Kingdom. The ethics committee of Royal Brompton Hospital/NHLI approved the study, and written informed consent was obtained from all volunteers. Any current employee identified from health surveillance registers as having had at least 1 month's contact with rat proteins was considered eligible. Each such employee was asked to complete a questionnaire, undergo skin

Results

At univariate analysis, cases were twice as likely to be atopic as referents (Table I). They were also more likely to have entered an animal housing facility on a daily basis, but they were less likely to have worked in the highest exposure job category. Rates of sensitization differed among the 6 sites. The prevalence of work-related chest symptoms was much higher among those sensitized (42% vs 3%).

The distributions of HLA genotypes by case status are shown in Table II; shown alongside, for

Discussion

To date, this is the largest study of HLA associations with specific symptoms and sensitization to a single species of laboratory animal. Sensitized individuals were twice as likely to be HLA-DRβ1*07-positive and half as likely to be HLA-DRβ1*03-positive. These associations were independent of age, sex, and broad indicators of exposure. HLA-DRβ1*07 was also, and more strongly, independently associated with work-related chest symptoms. Among employees similarly exposed to rats in their work,

Acknowledgements

We thank the management and staff at each survey site for allowing the department to undertake surveys on their premises, and we thank all of the individuals who carried out the fieldwork. We also thank the National Asthma Campaign for funding this work.

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This work was funded by the National Asthma Campaign.

☆☆

Reprint requests: Meinir G Jones, PhD, Department of Occupational and Environmental Medicine, Faculty of Medicine, Imperial College (NHLI), 1B Manresa Rd, London SW3 6LR, United Kingdom.

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