Mouse IgE test

Hilton, J., et al., The mouse IgE test for the identification of potential chemical respiratory allergens considerations of stability and controls, J. Appl. Toxicol., 16, 165, 1996. 

Hilton, J. et al., Identification of chemical respiratory allergens Dose response relationships in the mouse IgE test. Toxicol. Methods, 5, 51, 1995. 

Dearman, R.J. et al., The mouse IgE test Interlaboratory evaluation and comparison of BALB/c and C57B1/6 strain mice. Toxicol. Methods, 8, 69, 1998. 

The qualities of immune responses stimulated by DNCB and TMA were considered to be indicative of the selective activation of distinct populations of T-helper (Th) cells, with DNCB and TMA eliciting, respectively, preferential Thl cell-type and Th2 cell-type responses. Similarly divergent immune responses were observed following the topical exposure of mice to other known or suspected chemical contact and respiratory allergens and in each case only those chemicals believed to cause sensitization of the respiratory tract were found to stimulate an increase in the serum concentration of IgE (Dearman and Kimber, 1992 Dearman et al., 1992d). The association between the potential to cause respiratory allergy in humans and the ability to induce in mice an increase in serum IgE concentration forms the basis of the mouse IgE test described below. 

Dose selection for the mouse IgE test is an important issue. In practice the policy currently is to examine test chemicals first in the local lymph node assay, a mouse predictive test for the identification of contact allergens (Kimber and Basketter, 1992 Kimber et al., 1994). Wherever possible application concentrations are selected for use in the mouse IgE test that elicit a positive... 

During the course of investigations of the mouse IgE test, responses induced by TMA and DNCB have been measured concurrently in over 15 independent experiments. The test concentrations chosen for such comparisons (25 per cent TMA and 1 per cent DNCB) were selected as those that were found to be of equivalent immunogenicity in BALB/c strain mice with respect to the stimulation of draining lymph node cell proliferative responses. In all experiments the concentration of serum IgE recorded following exposure of mice to TMA was increased significantly compared with levels measured in sera drawn from animals treated concurrently with vehicle alone or with DNCB. In no instance did DNCB cause an increase in serum IgE levels relative... 

To date there is little confirmatory evidence available from independent laboratories regarding the sensitivity and selectivity of the mouse IgE test, although Potter and Wederbrand (1995) have recently reported similar, although not identical, results using BALB/c strain mice. Of interest also are preliminary data that indicate a rat variant of the mouse IgE test may be achievable. It was shown that topical exposure to TMA, but not DNCB, elicited an increase in the serum concentration of IgE in Brown Norway rats (Arts et al., 1995). 

Figure 7.2 Schema illustrating current protocol for conduct of a mouse IgE test, incorporating 25 per cent TMA (positive control) and 1 per cent DNCB (negative control).

In summary, the mouse IgE test provides a novel and, to date, promising alternative method for the predictive identification of potential chemical respiratory allergens. The requirements now are for a more extensive evaluation of the assay with a wider range of test chemicals and for an examination of the method in independent laboratories. 

While the use of IgGl as an immunogenicity endpoint to attempt to predict the relative allergenicity of enzymes/proteins is open to criticism as mechanistically irrelevant, the true value of the method will lie in its performance relative to other preclinical test methods and human sensitization patterns. Many newly emerging methods in immunoloxicology rely on surrogate endpoints or endpoints that measure only a component of the response process (e.g. skin equivalent cultures for skin and eye irritation, local lymph node assay for contact sensitization, mouse IgE test for chemical respiratory sensitization). Their value lies in their... 

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