Summary A survey of the prevalence of laboratory animal allergy to rats, mice, guinea pigs and rabbits among sixty‐nine animal workers and 308 other subjects on a pharmaceutical research site revealed a 22% prevalence of laboratory animal allergy among the animal workers. The overall prevalence of atopy was 67% in persons with allergy to laboratory animals. This was significantly greater than the 31% prevalence in other animal workers. Skin‐prick tests and specific IgG and IgE assays to urinary protein extracts strongly correlated with the occurrence of laboratory‐animal allergy and would appear to have diagnostic value. However, a number of clinically diagnosed laboratory‐ani‐mal‐allergy subjects gave no evidence of immunological response to the urinary allergens and wider diagnoses may have to be applied in these cases.

Casella Simquad air samplers, with 0·5 mu;M cut-off filters, were employed to sample the air in a laboratory animal house environment. The extracts obtained were assayed for laboratory animal urinary protein allergens using the inhibition radioallergosorbent test (RAST inhibition). The results showed that the collection and assay methods were of value and studies were extended to the influence of air change rates and humidity on airborne allergen levels. Reducing the air changes increased allergen levels, whilst increasing the humidity from 54% to 77% caused a significant reduction in allergen levels.

Human IgG antibody subclasses have been measured in the sera of workers exposed to rats, using a crude extract of rat urinary protein antigens, in an ELISA system. The antibody titres in individuals either with or without specific IgE were similar, with the exception of IgG4 where the mean level of this subclass was lower in those individuals with measurable titres of IgE (p < 0.01). Symptomatic individuals, with specific IgE, also had lower titres of IgG4 than the corresponding asymptomatic, IgE-positive subjects (p < 0.05). The frequency of positives in each subclass assay was similar in both groups. These findings suggest that higher levels of IgG4 may have a protective role.

Radioallergosorbent tests (RAST) using urinary proteins from mice, rats, guinea pigs and rabbits have been developed and used in the diagnosis of laboratory animal allergy (LAA). Of the 273 subjects tested, 15 had been previously diagnosed as laboratory animal allergic and 8 of these (53%) gave one or more positive RAST results. Of the 258 symptom-free individuals, only 9 (3.5%) had one or more positive RAST. Of these 9, 7 had previously worked with animals or had occupational exposure to the appropriate species; the remaining 2 individuals had only some pet exposure. RAST was, therefore, of value in the diagnosis of LAA. During the development of these RAST assays, several sources of potential error were identified. Modest titres of total IgE (600 IU/ml and above) were found to influence the specific RAST index observed and lead to false positive results. The presence of human IgG antibody specific for rabbit serum proteins was also identified in four sera, and was responsible for interference in the rabbit urinary protein RAST system.

Summary A major complication of in vivo monoclonal antibody therapy in patients with cancer is the host's immune response to the administered xenogeneic immunoglobulin. We have performed parallel clinical and experimental studies to investigate the possibility that deaggregation of the therapeutic monoclonal antibody might render it non-immunogenic, or even tolerogenic, as has been suggested in several animal studies. Deaggregation of xenogeneic immunoglobulin has been shown by others to induce non-responsiveness in some ('susceptible') but not in other ('resistant') strains of mice. We have used an improved deaggregation method of size exclusion chromatography connected to FPLC and have developed a sensitive ELISA detection system to determine whether highly purified human immunoglobulin G (hIgG) monomers could be tolerogenic even to 'resistant' mice. However, our data show that all preparations of hIgG are immunogenic to 'resistant' mice, and that although deaggregation does significantly reduce the anti-hIgG response of 'susceptible' strains, tolerance is not induced. Concommitant administration of cyclosporin A and deaggregated hIgG had a additive effect in reducing the murine anti-hIgG secondary response. In clincial studies of patients with ovarian cancer who received in vivo immunotherapy with either iodine-131 (not aggregated) or yttrium-90 (aggregated) HMFGI mouse monoclonal antibody, no significant difference was found between the immune responses to aggregated and non-aggregated murine immunoglobulin G. Our data suggest that deaggregation alone is unlikely to be useful in controlling the human anti-murine immunoglobulin G response in our outbred patient population, although in combination with an immunosuppressant it may be more effective.