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

Clin Chim Acta. 2000 Jan 20;291(1):53-66. doi: 10.1016/s0009-8981(99)00199-0.

Abstract

An immunoprecipitation assay for autoantibodies (Abs) to the human islet cell antigen IA-2 has been developed using 125I-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 125I-labelled IA-2 showed a good correlation with the results of an immunoprecipitation assay based on 35S-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 125I-labelled recombinant IA-2 showed good sensitivity, precision and specificity which, combined with an easy and convenient protocol, makes it attractive for routine use.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Autoantibodies / blood*
  • Autoantigens / immunology*
  • Child
  • Child, Preschool
  • Diabetes Mellitus, Type 1 / immunology*
  • Diabetes Mellitus, Type 2 / immunology
  • Female
  • Glutamate Decarboxylase / immunology
  • Humans
  • Immunosorbent Techniques*
  • Infant
  • Insulin / immunology
  • Islets of Langerhans / immunology
  • Male
  • Membrane Glycoproteins / immunology*
  • Membrane Proteins*
  • Middle Aged
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Protein Tyrosine Phosphatases / immunology*
  • Receptor-Like Protein Tyrosine Phosphatases, Class 8

Substances

  • Autoantibodies
  • Autoantigens
  • Insulin
  • Membrane Glycoproteins
  • Membrane Proteins
  • PTPRN2 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Protein Tyrosine Phosphatases
  • Receptor-Like Protein Tyrosine Phosphatases, Class 8
  • Glutamate Decarboxylase