'Insulin autoantibody affinity measurement using a single concentration of unlabelled insulin competitor discriminates risk in relatives of patients with type 1 diabetes

Clin Exp Immunol. 2012 Jan;167(1):67-72. doi: 10.1111/j.1365-2249.2011.04495.x.


Development of high-risk combinations of multiple islet autoantibodies and type 1 diabetes is associated with high-affinity insulin autoantibodies (IAA), but IAA affinity measurements require large serum volumes. We therefore investigated whether a simplified method of IAA affinity measurement using a low concentration of unlabelled insulin (ULI) competitor discriminated between moderate-high- and low-affinity IAA and identified individuals at highest risk of disease. Samples were assayed by radiobinding microassay using high (4·0 × 10(-5) mol/l) and low (7 × 10(-9) mol/l) ULI concentrations for competitive displacement in three cohorts of IAA-positive individuals; (1) 68 patients with newly-diagnosed type 1 diabetes; (2) 40 healthy schoolchildren; and (3) 114 relatives of patients with type 1 diabetes followed prospectively for disease development (median follow-up 13 years). IAA results obtained with low ULI were expressed as a percentage of those obtained with high ULI and this was used to classify samples as low or moderate-high affinity (0-50% and >50%, respectively). Sixty-eight patient samples were positive with high and 67 (99%) with low ULI. Forty schoolchildren were IAA-positive with high and 22 (55%) with low ULI (P < 0·001). Of the relatives, 113 were positive with high and 83 (73%) with low ULI (P < 0·001). In relatives, moderate-high affinity IAA were associated with multiple islet antibodies (P < 0·001) and greater diabetes risk than low affinity IAA (P < 0·001). A single low concentration of ULI competitor can act as a surrogate for complex IAA affinity measurements and identifies those IAA-positive relatives at highest risk of disease progression.

Publication types

  • Comparative Study
  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antibody Affinity*
  • Autoantibodies / blood
  • Autoantibodies / immunology*
  • Autoantigens / immunology*
  • Binding, Competitive
  • Child
  • Child, Preschool
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 1 / immunology*
  • Family Health
  • Female
  • Follow-Up Studies
  • Glutamate Decarboxylase / immunology
  • Humans
  • Insulin / immunology*
  • Islets of Langerhans / immunology
  • Male
  • Middle Aged
  • Prospective Studies
  • Radioimmunoassay / methods*
  • Risk
  • Young Adult


  • Autoantibodies
  • Autoantigens
  • Insulin
  • Glutamate Decarboxylase