Rat-specific IgG and IgG4 antibodies associated with inhibition of IgE-allergen complex binding in laboratory animal workers

Objectives 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 IgG(4) antibodies. We set out to examine whether the increased levels of rat-specific IgG and IgG(4) 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/G(4) 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.