title: Induction of diabetes-related autoantibodies below cutoff for "positivity" in young nondiabetic children.
abstract: The aim was to study the natural course of diabetes-related autoantibodies at low concentrations, below "positivity", in a nondiabetic population followed up from infancy. Blood samples were taken from 205 children at 6 weeks, 6 months, 18 months, and 5 years of age. Autoantibodies against GAD(65) (GADA), tyrosine phosphatase (IA-2A), and insulin (IAA) were determined by radioligand-binding assays. All children had detectable levels of GADA and approximately half had IA-2A, but only approximately 10% had detectable levels of IAA during the follow-up period. Many children developed IA-2A already at 6 months of age, similar concentrations were seen at 18 months, and then the levels of IA-2A decreased until 5 years of age. GADA were induced less often at 6 months of age, increased up to 18 months, and fluctuated at similar levels up to 5 years of age. IAA were detectable in so few children and at low levels, so no trend in natural course could be revealed. We conclude that there is a natural induction of humoral immune response to beta cell autoantigens early in life. Our results suggest that the mechanisms of beta cell tolerance to GAD and IA-2 differ in healthy children.
authors.affiliation: Department of Molecular and Clinical Medicine, Division of Pediatrics, Clinical Research Center, Faculty of Health Sciences, Linköping University, Linköping, Sweden. hanna.holmberg@imk.liu.se
authors.forename: Hanna
authors.initials: H
authors.lastname: Holmberg
authors.forename: Outi
authors.initials: O
authors.lastname: Vaarala
authors.forename: Karin
authors.initials: K
authors.lastname: Fälth-Magnusson
authors.forename: Johnny
authors.initials: J
authors.lastname: Ludvigsson
mesh_terms: D001323:Autoantibodies / Q000096:biosynthesis* / Q000276:immunology; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005968:Glutamate Decarboxylase / Q000276:immunology; D006801:Humans; D007223:Infant; D007328:Insulin / Q000276:immunology; D007527:Isoenzymes / Q000276:immunology; D011446:Prospective Studies; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000276:immunology; D011869:Radioligand Assay; D012680:Sensitivity and Specificity
chemical_list: D001323:Autoantibodies; D007328:Insulin; D007527:Isoenzymes; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2