title: 'Insulin autoantibody affinity measurement using a single concentration of unlabelled insulin competitor discriminates risk in relatives of patients with type 1 diabetes.
abstract: 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.
authors: School of Clinical Sciences, University of Bristol, Southmead Hospital, Bristol, UK.
authors: R M
authors: RM
authors: Curnock
authors: C R
authors: CR
authors: Reed
authors: S
authors: S
authors: Rokni
authors: J W
authors: JW
authors: Broadhurst
authors: P J
authors: PJ
authors: Bingley
authors: A J K
authors: AJ
authors: Williams
mesh_terms: D000293:Adolescent; D000328:Adult; D000915:Antibody Affinity; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D001667:Binding, Competitive; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology*; D005192:Family Health; D005260:Female; D005500:Follow-Up Studies; D005968:Glutamate Decarboxylase / Q000276:immunology; D006801:Humans; D007328:Insulin / Q000276:immunology*; D007515:Islets of Langerhans / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011863:Radioimmunoassay / Q000379:methods*; D012306:Risk; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D007328:Insulin; D005968:Glutamate Decarboxylase