title: Stratification of type 1 diabetes risk on the basis of islet autoantibody characteristics.
abstract: Family history of type 1 diabetes and autoantibodies to the islet antigens insulin (IAA), glutamate decarboxylase (GADA), and the protein tyrosine phosphatase-like protein IA-2 (IA-2A) are strong predictors of type 1 diabetes, but the rate of progression to diabetes in multiple islet autoantibody-positive relatives varies widely. We asked whether detailed characterization of islet autoantibodies that included determination of titer, epitope specificity, and IgG subclass would improve diabetes prediction in a large cohort of autoantibody-positive relatives. The study shows a strong association between risk and high titer, broad antibody responses to IA-2 and insulin. The highest risks were associated with high-titer IA-2A and IAA, IgG2, IgG3, and/or IgG4 subclass of IA-2A and IAA, and antibodies to the IA-2-related molecule IA-2beta. Using models based on these antibody characteristics, autoantibody-positive relatives can be classified into groups with risks of diabetes ranging from 7 to 89% within 5 years.
authors.affiliation: Diabetes Research Institute and 3rd Medical Department, Hospital München-Schwabing, Munich, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Achenbach
authors.forename: Katharina
authors.initials: K
authors.lastname: Warncke
authors.forename: Jürgen
authors.initials: J
authors.lastname: Reiter
authors.forename: Heike E
authors.initials: HE
authors.lastname: Naserke
authors.forename: Alistair J K
authors.initials: AJ
authors.lastname: Williams
authors.forename: Polly J
authors.initials: PJ
authors.lastname: Bingley
authors.forename: Ezio
authors.initials: E
authors.lastname: Bonifacio
authors.forename: Anette-G
authors.initials: AG
authors.lastname: Ziegler
mesh_terms: D000293:Adolescent; D001323:Autoantibodies / Q000097:blood*; D003922:Diabetes Mellitus, Type 1 / Q000145:classification / Q000453:epidemiology* / Q000235:genetics / Q000276:immunology*; D005190:Family; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007330:Insulin Antibodies / Q000097:blood*; D008297:Male; D015999:Multivariate Analysis; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D001323:Autoantibodies; C096322:ICA512 autoantibody; D007074:Immunoglobulin G; D007330:Insulin Antibodies; C024211:islet cell antibody; D005968:Glutamate Decarboxylase