Intradermal administration of GAD & evaluation of diabetes incidence in mice: Possible relevance for skin tests in humans

In vitro cell mediated reactivity to Glutamic Acid Decarboxylase (GAD) has been reported in man and in the non-obese diabetic (NOD) mouse. The demonstration of such reactivity in vivo using GAD in a simple intradermal skin test would be useful for mass screening of subjects at risk of Type 1 diabetes. Such a skin test could be simply applied to the forearm, then signs of local reaction would indicate patients at risk. However, in order to safely apply a skin test of this type it must be certain that administration of the antigen does not itself provoke or start the process leading to diabetes in susceptible individuals. In the present study the NOD mouse model was used. GAD and two peptides of GAD, which may have relevance to the disease process, were applied intradermally to these mice to determine whether a local reaction could be seen and to see if the diabetes rate was altered. Moreover, Balb/c mice, which can be considered to be at zero risk of developing the disease, were also injected with the same GAD and GAD peptides, No significant differences were seen in the diabetes incidence of the treatment groups compared to the control groups in either the NOD or Balb/c mice although a local swelling was seen in female NOD mice susceptible to diabetes after GAD administration in the footpad. We conclude that the administration of GAD and/or GAD peptides does not provoke or accelerate diabetes incidence in the NOD mouse and that an intradermal skin-test with GAD may be suitable for preliminary trials aimed at large scale screening of humans for their potential to develop type 1 diabetes.