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.

Demonstration of natural autoantibodies against the neurofilament protein α-internexin in sera of patients with endocrine autoimmunity and healthy individuals

“…It has been shown that the levels and reactivity profiles of NAAbs are prone to alterations in human disease, both autoimmune and nonautoimmune [24]. On the other hand, AAbs associated with autoimmune disease have been also demonstrated at low levels in healthy subjects [25]. In this study, despite the high overall frequency of serum ␣-INX AAbs, variable AAb levels were detected in individual sera, and even more, IgM ␣-INX AAb levels were increased in patients with idiopathic hypopituitarism.…”

The importance of CTLA-4 polymorphism and human leukocyte antigen genotype for the induction of diabetes-associated cytokine response in healthy school children

“…GAD 65 (GADA) and IA‐2 (IA‐2A) autoantibody titers were determined from serum samples using an immunoprecipitaton assay (35), and insulin autoantibodies (IAA) were measured using a radioimmunoassay described in detail elsewhere (36).…”