title: DPD epitope-specific glutamic acid decarboxylase (GAD)65 autoantibodies in children with Type 1 diabetes.
abstract: To study whether DPD epitope-specific glutamate decarboxylase autoantibodies are found more frequently in children with milder forms of Type 1 diabetes.
  
  
  
  We prospectively evaluated 75 children with new-onset autoimmune Type 1 diabetes, in whom we collected demographic, anthropometric and clinical data and measured islet autoantibodies. Glutamate decarboxylase 65 autoantibody-positive samples were analysed for epitope specificities using recombinant Fab against the DPD-defined epitope of glutamate decarboxylase 65.
  
  
  
  After adjustment for age, positive DPD epitope recognition was significantly associated with higher C-peptide levels at onset (P = 0.02, r2=0.21, n = 35), and high DPD recognition in the highest quartile tended to be associated with HbA1c≤ 53 mmol/mol (7%) at the last follow-up [mean (sd) follow-up 1.3 (0.4) years; P = 0.07; for the model, P = 0.044, n = 30)]. Age- and sex-adjusted BMI percentile was significantly correlated with recognition of the DPD-defined epitope (P < 0.03, r2=0.14, n = 34), but this correlation was driven by the older age group (age ≥ 10 years; P = 0.016, r2=0.27, n = 21) and was not significant in younger children (P = 0.93, n = 13). There were no independent associations with sex, race/ethnicity, diabetic ketoacidosis, HbA1c, HLA DR3-DQ2/DR4-DQ8 or autoantibody number.
  
  
  
  Our findings suggest that recognition of the DPD-defined glutamate decarboxylase 65 autoantibody epitope at Type 1 diabetes onset is directly associated with β-cell function, BMI and age, which supports the hypothesis that immunological factors contribute to the clinical heterogeneity of Type 1 diabetes. Larger studies relating epitope-specific glutamate decarboxylase 65 autoantibody to clinical phenotype in children with Type 1 diabetes are warranted.
authors.affiliation: Department of Pediatrics, Section of Diabetes and Endocrinology, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA.
authors.forename: N
authors.initials: N
authors.lastname: Bansal
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: C S
authors.initials: CS
authors.lastname: Hampe
authors.affiliation: Department of Pediatrics, Section of Pediatric Endocrinology, Children's Hospital of San Antonio, Baylor College of Medicine, San Antonio, TX, USA.
authors.forename: L
authors.initials: L
authors.lastname: Rodriguez
authors.affiliation: Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX, USA.
authors.forename: E
authors.initials: E
authors.lastname: O'Brian Smith
authors.affiliation: Department of Pediatrics, Section of Diabetes and Endocrinology, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA.
authors.forename: J
authors.initials: J
authors.lastname: Kushner
authors.affiliation: Translational Metabolism Unit, Diabetes Research Center, Division of Diabetes, Endocrinology and Metabolism, Baylor College of Medicine, Houston, TX, USA.
authors.forename: A
authors.initials: A
authors.lastname: Balasubramanyam
authors.affiliation: Department of Pediatrics, Section of Diabetes and Endocrinology, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Redondo
mesh_terms: D000293:Adolescent; D000918:Antibody Specificity; D001323:Autoantibodies / Q000097:blood* / Q000737:chemistry; D002096:C-Peptide / Q000097:blood; D027682:Cation Transport Proteins / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D005260:Female; D005968:Glutamate Decarboxylase / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D007223:Infant; D008297:Male; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8 / Q000276:immunology; D000075703:Zinc Transporter 8
chemical_list: D001323:Autoantibodies; D002096:C-Peptide; D027682:Cation Transport Proteins; D000939:Epitopes; C492522:SLC30A8 protein, human; D000075703:Zinc Transporter 8; C102889:PTPRN2 protein, human; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2