NUMBER OF AUTOANTIBODIES (AGAINST INSULIN, GAD OR ICA512 IA2) RATHER THAN PARTICULAR AUTOANTIBODY SPECIFICITIES DETERMINES RISK OF TYPE-I DIABETES/

We previously evaluated radioassays for insulin autoantibodies (IAA), glutamate decarboxylase autoantibodies (GAA) and ICA512bdc autoantibod ies (ICA512bdcAA) in the prediction of type I diabetes. Among first de gree relatives, the five year risk of diabetes was 0% if no autoantibo dy was positive, 15% if only one was positive, 44% if two were positiv e and 100% if ail three were positive. We measured IAA, GAA and ICA512 bdcAA in 45 patients with new onset type I diabetes (sampled within 7 days of insulin therapy), 882 first degree relatives of patients with type I diabetes, and 217 control subjects. ICA512bdc is a construct of the ICA512/IA2 molecule (amino acid residues 256-979), including the intracellular domain. Based on receiver-operating characteristic plots , there was no significant difference between the three assays in thei r ability to discriminate between disease and control subjects. The up per limits of normal for the assays were determined as the 99th percen tile of levels in the control subjects or higher. Using these cut-offs , 76% of new onset patients were positive for two or more autoantibodi es, and 98% were positive for one or more. In comparison, none of 198 control subjects tested for all three assays were positive for more th an one autoantibody. In relatives with a single autoantibody, or exact ly two autoantibodies, there was no difference in diabetes-free surviv al according to which one of the autoantibodies was present (P=0.70, l ogrank test), or which particular combination of autoantibodies was pr esent (P=0.56, logrank test) respectively. Our conclusions were as fol lows: the number of autoantibodies (counting IAA, GAA and ICA512bdcAA) is important in prediction, rather than the particular autoantibody s pecificities present. Among patients with new onset insulin-dependent diabetes, the absence of any of these autoantibodies justifies the con sideration of non-autoimmune forms of diabetes in the differential dia gnosis. (C) 1996 Academic Press Limited