GAD autoantibody epitope pattern after GAD-alum treatment in children and adolescents with type 1 diabetes

• Aims/hypothesis. Previously we have shown that two injections of glutamic acid decarboxylase formulated in alum (GAD-alum) preserved residual insulin secretion in children and adolescents with recent onset type 1 diabetes (T1D), and was accompanied by an increase in GAD autoantibody (GADA) titers. The aim of the present study was to investigate whether GAD-alum treatment affected the GADA epitope pattern. Methods. Serum samples of patients treated with GAD-alum (n=33) or placebo (n=27), at baseline and 1, 3, 9, and 15 months after initiation of treatment, were tested for their binding capacity to specific GADA epitopes in an epitope specific radioligand-binding assay with six GAD65-specific recombinant Fab (rFab) (b96.11, DPA, DPD, MICA3, b78 and N-GAD65 mAb). Results. For the period included in this study (baseline to 15 months) no difference in variability of binding to any of the tested rFab were observed. However, a higher median response to the b96.11-defined epitope in the first 3 months after the initial injection was observed in GAD-alum treated patients (-8.1%, min -72.4%, max 39.6%) compared to patients receiving placebo (1.5%, min -28.3%, max 28.6%) (p=0.02). This effect was especially evident in GAD-alum treated patients who experienced an increase of more than 100% in their GADA titer from baseline to 3 months (n=27), where we observed an 10.8% (-10.8%, min -72.4%, max 30.5%) increase in binding to the b96.11 epitope over the  first 3 months post initial injection (p=0.04). Subsequently the recognition of the b96.11-defined epitope in the GAD-alum group decreased between 3 and 15 months (8.3%, min -17.1%, max 36.7%) compared to the placebo group (-2.4%, min -32.8%, max 30.1%) (p<0.05) and returned to levels similar to that observed at baseline. Correlations between GADA titer and epitope binding for b96.11 and DPD were observed in the placebo group, but not in the GADalum group, at 3 and 15 months after initial treatment. Conclusions/interpretation. We conclude that administration of GAD-alum temporarily induced increased binding to one epitope specificity of GADA.

Nyckelord

Type 1 diabetes

autoantibody

epitope

GAD

MEDICINE

MEDICIN

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