Absence of avidity maturation of autoantibodies to the protein tyrosine phosphatase-like IA-2 molecule and glutamic acid decarboxylase (GAD65) during progression to type 1 diabetes

Immunoglobulin G avidity assays are used to distinguish between the acute and chronic phase of several infectious diseases, and there is evidence of autoantibody affinity maturation also in autoimmune diseases. To assess whether the analysis of the avidity of autoantibodies against the protein tyrosine phosphatase-like IA-2 molecule and glutamic acid decarboxylase (GAD65) could improve the accuracy of risk assessment of progression to clinical type 1 diabetes, we established methods for the determination of the autoantibody avidity based on our previously developed time-resolved fluorometric IA-2 and GAD65 autoantibody (IA-2A and GADA) assays. The avidity indices of sequential plasma samples from six IA-2A-positive and seven GADA-positive prediabetic children were analysed applying elution with urea and diethylamine (DEA). For comparison, corresponding avidity indices of control children, who have remained non-diabetic for at least 3 years after seroconversion to IA-2A and GADA positivity, were analysed. For most of the children, only a slight fluctuation in the avidity index values was observed over time, although the titres for IA-2A and GADA varied substantially in some cases. The avidity indices of the prediabetic children remained within the same range as those of the control group throughout the follow-up. Our results indicate that the analysis of the avidity index levels of IA-2A and GADA does not improve the accuracy of the prediction of type 1 diabetes based on autoantibody detection.