ICA512(IA-2) epitope specific assays distinguish transient from diabetes associated autoantibodies

J Autoimmun. 2002 Mar;18(2):191-6. doi: 10.1006/jaut.2001.0577.


ICA512/IA-2, a tyrosine phosphatase-like protein, is one of the major autoantigens in type 1 diabetes. Following phage display characterization of ICA512 autoantigenic epitopes, we developed fluid phase autoantibody radioimmunoassays for a series of ICA512 fragments (F1 [amino acids (aa): 761-964], F2A [aa 256-760], F2B [aa 761-928], and F2C [aa 929-979]). With the hypothesis that 'non-diabetes associated' ICA512 autoantibodies would differ from diabetes associated ICA512 autoantibodies in terms of epitopes recognized, we analyzed ten such serum samples (two from normal control individuals, one from a general population subject with transient ICA512 autoantibodies and seven from relatives of patients with type 1 diabetes who had single transient ICA512 positivity). All but one of the 'non-diabetes associated' ICA512 positive samples (9/10) did not react with Fragment 1 which contains the major antigenic epitopes of the molecule that were recognized by almost all (51/52) ICA512 positive new onset patient samples and pre-diabetic relatives (P< 10(-6)). The great majority of samples (44/52) from the new onset patients and pre-diabetic relatives reacted with at least two fragments and 60% (31/52) with three or more fragments. In contrast, only one sample of the ICA512 'non-diabetes associated' sera reacted with multiple fragments (P< 10(-4)). Our findings suggest that diabetes associated anti-ICA512 autoantibodies react with multiple ICA512 epitopes while non-diabetes associated ICA512 autoantibodies may usually represent reactivity of antibodies with determinants of ICA512 unrelated to type 1 diabetes. The ability to distinguish diabetes associated from non-diabetes associated anti-ICA512 autoantibodies should provide prognostic information and more importantly suggests that even with highly specific radioassays positivity may occur unrelated to type 1 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Autoantibodies / blood*
  • Autoantigens* / chemistry
  • Autoantigens* / genetics
  • Diabetes Mellitus, Type 1 / immunology*
  • Epitopes* / chemistry
  • Epitopes* / genetics
  • Humans
  • Islets of Langerhans / immunology
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology*
  • Models, Immunological
  • Peptide Fragments / chemistry
  • Peptide Fragments / genetics
  • Peptide Fragments / immunology
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Protein Tyrosine Phosphatases / chemistry
  • Protein Tyrosine Phosphatases / genetics
  • Protein Tyrosine Phosphatases / immunology*
  • Receptor-Like Protein Tyrosine Phosphatases, Class 8


  • Autoantibodies
  • Autoantigens
  • Epitopes
  • ICA512 autoantibody
  • Membrane Proteins
  • Peptide Fragments
  • PTPRN protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Protein Tyrosine Phosphatases
  • Receptor-Like Protein Tyrosine Phosphatases, Class 8