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A simplified method to assess affinity of insulin autoantibodies.
Clin. Immunol. 137, 415-421 (2010)
Insulin autoantibodies (IAA) precede type 1 diabetes, but not all IAA-positive children develop other islet autoantibodies and disease. Diabetes risk can be stratified by laborious IAA affinity measurement using competition with multiple ligand concentrations. Here, we identify a single competitor concentration that discriminates low- and high-affinity IAA. Discrimination was achieved among 122 IAA-positive sera using 7.0 nM competitor which is 54-fold that of the assay radioligand concentration. Relative-binding <60% at this competitor concentration identified all 85 sera with affinities ≥1.0×10⁸ L/mol and none with lower affinities (P<0.0001), and 45 (96%) of 47 multiple islet autoantibody-positive sera (P<0.0001). IAA competition was further tested in a second set of 119 IAA-positive sera. Of these, 99 fulfilled high-affinity competition criteria of <60% relative-binding at 7.0 nM competitor including 89 (94%) of 95 sera with multiple islet autoantibodies (P<0.0001). Thus, increased IAA specificity can be achieved with simple modification to existing assays.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Insulin autoantibody; Affinity; Type 1 diabetes; Prediction
ISSN (print) / ISBN
1521-6616
e-ISSN
1521-7035
Journal
Clinical Immunology
Quellenangaben
Volume: 137,
Issue: 3,
Pages: 415-421
Publisher
Elsevier
Publishing Place
San Diego, Calif
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Diabetes Research Type 1 (IDF)
Institute for Pancreatic Beta Cell Research (IPI)
Institute for Pancreatic Beta Cell Research (IPI)