title: Rat-specific IgG and IgG₄ antibodies associated with inhibition of IgE-allergen complex binding in laboratory animal workers.
abstract: OBJECTIVE
  The relationship between exposure to rodent allergens and laboratory animal allergy is complex; at highest allergen exposures there is an attenuation of sensitisation and symptoms which are associated with increased levels of rat-specific immunoglobulin (Ig)G and IgG4 antibodies. We set out to examine whether the increased levels of rat-specific IgG and IgG4 antibodies that we have previously observed at high allergen exposure in our cohort of laboratory animal workers play a functional role through blockage of the binding of IgE-allergen complex binding to CD23 receptors on B cells.
  
  
  METHODS
  Cross-sectional survey of laboratory animal workers (n=776) in six UK pharmaceutical companies were surveyed. IgE-allergen complex binding to B cells was measured in 703 (97.9%) eligible employees; their exposure was categorised by either job group or number of rats handled daily.
  
  
  RESULTS
  We observed a significant decrease in IgE-allergen complex binding to B cells with increasing quartiles of both rat-specific IgG and IgG4 antibodies (p<0.001). IgE-allergen complex binding to B cells was lower in workers with high allergen exposure, and significantly so (p=0.033) in the subgroup with highest exposures but no work-related chest symptoms.
  
  
  CONCLUSIONS
  These findings demonstrate a functional role for rat-specific IgG/G4 antibodies in laboratory animal workers, similar to that observed in patients treated with high dose immunotherapy who become clinically tolerant, suggesting a potential explanation for the attenuation of risk at highest allergen exposures.
authors.affiliation: Department of Occupational and Environmental Medicine, National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Jones
authors.affiliation: Department of Occupational and Environmental Medicine, National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: H
authors.initials: H
authors.lastname: Jeal
authors.affiliation: Department of Occupational and Environmental Medicine, National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: S
authors.initials: S
authors.lastname: Schofield
authors.affiliation: Department of Occupational and Environmental Medicine, National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: J M
authors.initials: JM
authors.lastname: Harris
authors.affiliation: Department of Allergy and Clinical Immunology, National Heart and Lung Institute, Imperial College London, part of the Medical Research Council and Asthma UK Centre for Allergic Mechanisms of Asthma, London, UK.
authors.forename: M H
authors.initials: MH
authors.lastname: Shamji
authors.affiliation: Department of Allergy and Clinical Immunology, National Heart and Lung Institute, Imperial College London, part of the Medical Research Council and Asthma UK Centre for Allergic Mechanisms of Asthma, London, UK.
authors.forename: J N
authors.initials: JN
authors.lastname: Francis
authors.affiliation: Department of Allergy and Clinical Immunology, National Heart and Lung Institute, Imperial College London, part of the Medical Research Council and Asthma UK Centre for Allergic Mechanisms of Asthma, London, UK.
authors.forename: S R
authors.initials: SR
authors.lastname: Durham
authors.affiliation: Department of Occupational and Environmental Medicine, National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: P
authors.initials: P
authors.lastname: Cullinan
mesh_terms: D000328:Adult; D000485:Allergens / Q000276:immunology*; D000704:Analysis of Variance; D017750:Animal Technicians; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D007073:Immunoglobulin E / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009784:Occupational Diseases / Q000276:immunology*; D016273:Occupational Exposure / Q000009:adverse effects*; D051381:Rats; D012882:Skin Tests; D006113:United Kingdom
chemical_list: D000485:Allergens; D007074:Immunoglobulin G; D007073:Immunoglobulin E