Check GAD antibody positivity with the Diamyd anti-GAD RIA plate*

Islet Cell Antibody Dependent Progression to Insulin Treatment in LADA Patientsnon-insulin requiring diabetes (%)age4510090807060504030201000 1 2 3 4(years)5 6The Search for Islet AntigensTDavid Leslie and Marco Londeihe search for islet antigens associatedwith the immuneresponse which precedes andpredicts the clinical onset ofType 1 diabetes received a substantialboost with the identificationof GAD as one the major antigens involvedin the aberrant immune response. We used a largecohort of identical twins which had been followedprospectively for several years to show for the firsttime that in these twins GAD antibodies were highlypredictive of progression to clinical diabetes.Further studies found that the isotypes of theseGAD antibodies were largely restricted to a singleisotype IgG1. In contrast, patients with a rare nervedisease Stiff Man Syndrome, who also have GADantibodies, and in whom about half the cases alsohave diabetes, were found to have a broad isotypeprofile involving antibody isotypes other than IgG1.These observations suggested that the antibodyimmune response to GAD in Type 1 diabetes showedmaturation at an early stage and was distinctfrom that found in Stiff Man Syndrome. We showedthat the T cell responses to GAD also differedin Type 1 diabetes as compared with normal subjectsand patients with Stiff man syndrome.Specifically, the dominant T cell response in diabeteswas to peptide epitopes (fragments) at the carboxy-“These studies, takentogether, suggest adistinct mature immune response toGAD involving cellular and humoralimmunity in Type 1 diabetes”terminal end of the GAD molecule. These studies,taken together, suggest a distinct mature immuneresponse to GAD involving cellular and humoralimmunity in Type 1 diabetes and raised the possibilitythat modulation of that response might modifythe destructive immune process associated with progressionto insulin dependence.The potential to modify that GAD immuneresponse and thereby modify the disease coursewas illustrated by others in animal models and isnow being tested in patients with autoimmunediabetes. Should these studies prove successful thenext stage would be to consider intervention in atrisksubjects since GAD antibodies, allied to otherdisease markers, are highly predictive of diseaseprogression.David Leslie, MD,FRCP., is Professor ofDiabetes and Autoimmunityat the RoyalLondon and St.Bartholomew´s Schoolof Medicine,University of London.Leslie has been involved in diabetes researchand clinical studies since 1975. Lesliehas been Director of the British DiabeticTwin Study since 1982, the world’s largesttwin study of its type. By studying twinsProfessor Leslie has been able to show thepossibilities for predicting and preventingdiabetes.Marco Londei, MD, isa Professor at theImperial CollegeSchool of Medicine inLondon, is one ofGreat Britain's mostinternationally renownedscientists in thefield of autoimmunity. Londei´s research hasbeen concentrated on T cells in autoimmunity.dmccad june 2003page 21