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首页> 外文期刊>Diabetic medicine: A journal of the British Diabetic Association >The first 142 amino acids of glutamate decarboxylase do not contribute to epitopes recognized by autoantibodies associated with Type 1 diabetes
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The first 142 amino acids of glutamate decarboxylase do not contribute to epitopes recognized by autoantibodies associated with Type 1 diabetes

机译：谷氨酸脱羧酶的前142个氨基酸不会有助于由与1型糖尿病相关的自身抗体识别的表位

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Abstract Aims Glutamate decarboxylase ( GAD ) antibodies are the most widely used predictive marker for Type 1 diabetes, but many individuals currently found to be GAD antibody‐positive are unlikely to develop diabetes. We have shown previously that radioimmunoassays using N‐terminally truncated 35 S‐ GAD 65 (96–585) offer better disease specificity with similar sensitivity to full‐length 35 S‐ GAD 65 (1–585). To determine whether assay performance could be improved further, we evaluated a more radically truncated 35 S‐ GAD 65 (143–585) radiolabel. Methods Samples from people with recent‐onset Type 1 diabetes ( n = 157) and their first‐degree relatives ( n = 745) from the Bart's–Oxford family study of childhood diabetes were measured for GAD antibodies using 35 S‐labelled GAD 65 (143–585). These were screened previously using a local radioimmunoassay with 35 S‐ GAD 65 (1–585). A subset was also tested by enzyme‐linked immunosorbent assay ( ELISA ), which performs well in international workshops, but requires 10 times more serum. Results were compared with GAD antibody measurements using 35 S‐ GAD 65 (1–585) and 35 S‐ GAD 65 (96–585). Results Sensitivity of GAD antibody measurement was maintained using 35 S‐ GAD 65 (143–585) compared with 35 S‐ GAD 65 (1–585) and 35 S‐ GAD 65 (96–585). Specificity for Type 1 diabetes was improved compared with 35 S‐ GAD 65 (1–585), but was similar to 35 S‐ GAD 65 (96–585). Relatives found to be GAD antibody‐positive using these truncated labels were at increased risk of diabetes progression within 15 years, compared with those positive for GAD (1–585) antibody only, and at similar risk to those found GAD antibody‐positive by ELISA . Conclusions The first 142 amino acids of GAD 65 do not contribute to epitopes recognized by Type 1 diabetes‐associated GAD antibodies. Low‐volume radioimmunoassays using N‐terminally truncated 35 S‐ GAD 65 are more specific than those using full‐length GAD 65 and offer practical alternatives to the GAD antibody ELISA for identifying children at increased risk of Type 1 diabetes.
机译：摘要目标谷氨酸脱羧酶（GAD）抗体是最广泛使用的1型糖尿病的预测标志物，但目前发现的许多人发现是GAD抗体阳性的不太可能发展糖尿病。我们以前所示，使用N-末端截短的35秒S-GAD 65（96-585）的放射免疫测定提供更好的疾病特异性，具有与全长35个S-GAD 65（1-585）相似的敏感性。为了确定是否可以提高测定性能，我们评估了一种更自由截断的35秒（143-585）放射性标记。方法使用35秒标记的GAD 65（ 143-585）。先前使用局部放射免疫测定与35秒（1-585）进行筛选。还通过酶联免疫吸附测定（ELISA）测试了一个亚特征，其在国际研讨会中表现良好，但需要血清的10倍。使用35s-GAD 65（1-585）和35s-GAD 65（96-585）将结果与GAD抗体测量进行比较。结果与35次S-GAD 65（1-585）和35次S-GAD 65（96-585）相比，使用35s-GAD 65（143-585）保持GAD抗体测量的敏感性。与35s-GAD 65（1-585）相比，改善了1型糖尿病患者的特异性，但与35s-GAD 65（96-585）相似。发现是GAD抗体阳性使用这些截短的标签的亲属在15年内增加了糖尿病进展的风险，而仅与GAD（1-585个）抗体的阳性相比，并且在ELISA发现GAD抗体阳性的类似风险。结论GAD 65的前142个氨基酸对1型糖尿病相关的GAD抗体识别的表位无贡献。使用n末端截短的35 S-GAD 65的低容量放射免疫测量比使用全长GAD 65的低容量放射免疫测量作用更具体，并且为GAD抗体ELISA提供实用的替代方案，用于鉴定儿童的1型糖尿病的风险增加。

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