Autoantibodies to IA-2 in insulin-dependent diabetes mellitus - Measurements with a new immunoprecipitation assay

An immunoprecipitation assay for autoantibodies (Abs) to the human islet cell antigen IA-2 has been developed using I-125-labelled recombinant IA-2 expressed in E. coli. With this assay IA-2 Abs were detected in 103/217 (47%) of IDDM patients of different ages and with different disease duration. IA-2 Ab prevalence was higher in younger patients (at the age of 15 years or below) with the recent onset IDDM (64/113; 57%) compared to patients above the age of 15 years (11/25; 44%). One of 40 (2.5%) Graves' disease patients and five of 204 (2.5%) of NIDDM patients were also positive. IA-2 Abs were not detected in sera from patients with Hashimoto's thyroiditis (n = 32), myasthenia gravis (n = 20) or systemic lupus erythematosus (n = 10). IA-2 Ab measurements based on I-125-labelled IA-2 showed a good correlation with the results of an immunoprecipitation assay based on S-35-labelled IA-2 produced in the in vitro transcription/translation system (r = 0.78; n = 113; p < 0.001). Out of 217 IDDM sera which were tested for IA-2 Abs, 140 (65%) were positive for Abs to glutamic acid decarboxylase (GAD) and 166 (76%) were positive for Abs to IA-2 and/or Abs to GAD, In addition, Abs to IA-2, to GAD and to insulin were analysed in sera from recent onset IDDM patients who had not been treated with insulin (n = 117). In all, 76/117 (65%) of these sera were positive for GAD Abs, 66/117 (56%) for IA-2 Abs, 45/117 (38%) for insulin Abs, However, 98/117 (84%) were positive for at least one of the three Abs confirming earlier observations on the complementarity of Ab testing in IDDM. Overall, the IA-2 Ab assay based on I-125-labelled recombinant IA-2 showed good sensitivity, precision and specificity which, combined with an easy and convenient protocol, makes it attractive for routine use. (C) 2000 Elsevier Science B.V. All rights reserved.