IA-2 combined epitope assay: a new, highly sensitive approach to evaluate IA-2 humoral autoimmunity in type 1 diabetes

Clin Immunol. 2005 Jun;115(3):260-7. doi: 10.1016/j.clim.2005.01.015.

Abstract

Islet tyrosine phosphatase 2 (IA-2) is one of the major autoantigens in type 1 diabetes. The aim of this work was to evaluate which IA-2 construct(s) among those usually employed has the highest sensitivity and specificity for detecting IA-2 autoantibodies in autoimmune diabetes and whether the combination of different IA-2 constructs into a single assay allows the detection of immunoreactivities otherwise not detectable by a single construct. For this purpose, we tested the single immunoreactivities of IA-2 FL(aa 1-979), IA-2(BDC)(aa 256-556:630-979), IA-2 IC(aa 605-979), IA-2(aa 256-760), IA-2(aa 761-928), and of 7 combinations of these fragments in the sera of 203 newly diagnosed type 1 diabetic patient (DM: 109 males,94 females, mean age 12.9 +/- 7.5 years) and 43 prediabetic subject (PDM: 20 males, 23 females, mean age 10.3 +/- 6.0 years) sera. IA-2 IC was the single construct that showed the highest sensitivity and specificity both in DM and PDM subjects; however, all of the other IA-2 constructs investigated detected additional immunoreactivities with respect to it. The combined use into the same assay of IA-2 IC, IA-2 FL, and IA-2 (256-760) constructs allowed detection of IA-2 Abs in additional 13.3% DM and 30.4% PDM subjects compared to the single IA-2 IC construct, suggesting this methodology as a new, highly sensitive approach to the study of IA-2 autoimmunity in type 1 diabetes.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Amino Acid Sequence
  • Autoantibodies / immunology
  • Autoimmunity
  • Base Sequence
  • Biomarkers / blood
  • Child
  • Diabetes Mellitus, Type 1 / diagnosis*
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 1 / immunology
  • Epitopes / analysis*
  • Epitopes / genetics
  • Epitopes / immunology
  • Female
  • Humans
  • Male
  • Membrane Proteins / analysis
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology*
  • Molecular Sequence Data
  • Protein Phosphatase 2
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Protein Tyrosine Phosphatases / analysis
  • Protein Tyrosine Phosphatases / genetics
  • Protein Tyrosine Phosphatases / immunology*
  • Receptor-Like Protein Tyrosine Phosphatases, Class 8
  • Sensitivity and Specificity

Substances

  • Autoantibodies
  • Biomarkers
  • Epitopes
  • Membrane Proteins
  • Protein Phosphatase 2
  • PTPRN2 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Protein Tyrosine Phosphatases
  • Receptor-Like Protein Tyrosine Phosphatases, Class 8