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.
RCT Entities:
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.
Authors: S Baekkeskov; H J Aanstoot; S Christgau; A Reetz; M Solimena; M Cascalho; F Folli; H Richter-Olesen; P De Camilli; P D Camilli Journal: Nature Date: 1990-09-13 Impact factor: 49.962
Authors: L K Gilliam; K A Binder; J P Banga; A-M Madec; E Ortqvist; I Kockum; D Luo; C S Hampe Journal: Clin Exp Immunol Date: 2004-11 Impact factor: 4.330
Authors: W Richter; J Endl; T H Eiermann; M Brandt; R Kientsch-Engel; C Thivolet; H Jungfer; W A Scherbaum Journal: Proc Natl Acad Sci U S A Date: 1992-09-15 Impact factor: 11.205
Authors: Carolyn J Padoa; J Paul Banga; Anne-Marie Madec; Manfred Ziegler; Michael Schlosser; Eva Ortqvist; Ingrid Kockum; Jerry Palmer; Olov Rolandsson; Katherine A Binder; Jefferson Foote; Dong Luo; Christiane S Hampe Journal: Diabetes Date: 2003-11 Impact factor: 9.461