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GAD autoantibody epitope pattern after GAD‐alum treatment in children and adolescents with type 1 diabetes
Author(s) -
Skoglund Camilla,
Chéramy Mikael,
Casas Rosaura,
Ludvigsson Johnny,
Hampe Christiane S
Publication year - 2012
Publication title -
pediatric diabetes
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.678
H-Index - 75
eISSN - 1399-5448
pISSN - 1399-543X
DOI - 10.1111/j.1399-5448.2011.00802.x
Subject(s) - epitope , type 1 diabetes , autoantibody , medicine , glutamate decarboxylase , alum , placebo , diabetes mellitus , immunology , antibody , endocrinology , biochemistry , biology , chemistry , pathology , enzyme , alternative medicine , organic chemistry
Skoglund C, Chéramy M, Casas R, Ludvigsson J, Hampe CS. GAD autoantibody epitope pattern after GAD‐alum treatment in children and adolescents with type 1 diabetes. Aims: We have previously 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 increased GAD autoantibody (GADA) titers. The aim of this study was to investigate whether GAD‐alum treatment affected the GADA epitope pattern. Methods: Serum samples from patients treated with GAD‐alum (n = 33) or placebo (n = 27), at baseline, 1, 3, 9, and 15 months after the initial injection, were tested for their binding capacity to specific GADA epitopes in an epitope‐specific radioligand binding assay with six recombinant Fab (rFab) (b96.11, DPA, DPD, MICA3, b78, and N‐GAD 65 mAb). Results: No significant differences in variability of binding to any of the tested rFab were observed from baseline to 15 months. There was a sustained low binding of GADA to the b78‐ and N‐GAD 65 mAb‐defined epitopes, often recognized by GADA in patients with stiff person syndrome (SPS) and seldom in T1D patients. However, binding of GADA to the T1D‐associated b96.11‐defined epitope increased between baseline and 3 months in GAD‐alum (−8.1%, min −72.4%, max 39.6%) compared to placebo patients (1.5%, min −28.3%, max 28.6%) (p = 0.02). Subsequently, the b96.11‐defined epitope recognition returned to levels similar to that observed at baseline. Conclusions: GAD‐alum injections did not affect binding of GADA to SPS‐related epitopes, further supporting the safety of the treatment. There were no changes in GADA epitope specificity to the T1D‐related epitopes, except for a temporarily increased binding to one of the tested epitopes.