title: Stable GAD65 autoantibody epitope patterns in type 1 diabetes children five years after onset.
abstract: Autoantibodies to GAD65 (GAD65Ab) are prominent in type 1 diabetes. These autoantibodies may be present both years before and after the clinical diagnosis of type 1 diabetes and are widely used as a marker for the disease. Recently it has been demonstrated that progression to type 1 diabetes is accompanied by GAD65Ab epitope maturation. Here we examine whether autoantibody maturation processes also progress after the clinical diagnosis of type 1 diabetes. Antibody reactivity to GAD65, GAD67 and GAD65/67 fusion proteins was measured by radioimmunoassays in 62 children with type 1 diabetes. Samples were taken at diagnosis and five years later. While the overall GAD65Ab level declined over time, the epitope pattern was remarkably stable with no significant changes in binding pattern. Loss of GAD65Ab-positivity was associated with significantly lower GAD65Ab indices at diagnosis compared to patients' sera that remained GAD65Ab-positive. The decrease in GAD65Ab levels did not correlate to residual C-peptide levels. Our data suggest that processes controlling GAD65Ab levels and epitope binding patterns remain stable during the first five years of type 1 diabetes.
authors.affiliation: Robert H. Williams Laboratory, Department of Medicine, Box 357710, University of Washington, Seattle 98195-7710, USA. champe@u.washington.edu
authors.forename: Christiane S
authors.initials: CS
authors.lastname: Hampe
authors.forename: Lisa P
authors.initials: LP
authors.lastname: Hammerle
authors.forename: Lynn
authors.initials: L
authors.lastname: Bekris
authors.forename: Eva
authors.initials: E
authors.lastname: Ortqvist
authors.forename: Bengt
authors.initials: B
authors.lastname: Persson
authors.forename: Ake
authors.initials: A
authors.lastname: Lernmark
mesh_terms: D000293:Adolescent; D000328:Adult; D000918:Antibody Specificity / Q000276:immunology; D001323:Autoantibodies / Q000096:biosynthesis / Q000378:metabolism*; D015415:Biomarkers; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000175:diagnosis / Q000201:enzymology* / Q000276:immunology*; D000939:Epitopes / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D007223:Infant; D007527:Isoenzymes / Q000235:genetics / Q000276:immunology*; D010641:Phenotype; D011863:Radioimmunoassay; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D012307:Risk Factors
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D000939:Epitopes; D007527:Isoenzymes; D011994:Recombinant Proteins; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; C401141:glutamate decarboxylase 2