Stratification of type 1 diabetes risk on the basis of islet autoantibody characteristics.
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.
Achenbach
Peter
P
Diabetes Research Institute and 3rd Medical Department, Hospital München-Schwabing, Munich, Germany.
Warncke
Katharina
K
Reiter
Jürgen
J
Naserke
Heike E
HE
Williams
Alistair J K
AJ
Bingley
Polly J
PJ
Bonifacio
Ezio
E
Ziegler
Anette-G
AG
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
D001323:Autoantibodies; C096322:ICA512 autoantibody; D007074:Immunoglobulin G; D007330:Insulin Antibodies; C024211:islet cell antibody; D005968:Glutamate Decarboxylase