Division of Pediatrics & Diabetes Research Centre, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Pediatr Diabetes. 2012 May;13(3):244-50. doi: 10.1111/j.1399-5448.2011.00802.x. Epub 2011 Aug 16.
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.
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).
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.
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.
我们之前的研究表明，在新诊断的 1 型糖尿病（T1D）患儿和青少年中，两次注射谷氨酸脱羧酶与明矾（GAD-明矾）联合治疗可保留残余的胰岛素分泌，并伴有谷氨酸脱羧酶自身抗体（GADA）滴度的增加。本研究旨在探讨 GAD-明矾治疗是否影响 GADA 表位模式。
用表位特异性放射性配体结合试验检测基线、初次注射后 1、3、9 和 15 个月接受 GAD-明矾（n=33）或安慰剂（n=27）治疗的患者血清样本与六种重组 Fab（rFab）（b96.11、DPA、DPD、MICA3、b78 和 N-GAD（65）mAb）的结合能力。
从基线到 15 个月，与任何测试的 rFab 的结合变异性均无显著差异。GADA 对 b78 和 N-GAD（65）mAb 定义的表位的结合持续低，这些表位通常被僵硬人综合征（SPS）患者的 GADA 识别，而在 T1D 患者中很少被识别。然而，与安慰剂患者（1.5%，最小-28.3%，最大 28.6%）相比，GAD-明矾治疗组 GADA 与 T1D 相关的 b96.11 定义表位的结合在基线至 3 个月期间增加（-8.1%，最小-72.4%，最大 39.6%）（p=0.02）。随后，b96.11 定义的表位识别恢复到与基线观察到的水平相似。
GAD-明矾注射治疗不会影响 GADA 与 SPS 相关表位的结合，进一步支持该治疗的安全性。除了一个测试表位的结合暂时增加外，GADA 对 T1D 相关表位的表位特异性没有变化。
