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对N端截短的GAD65(96-585)的反应性可识别出与1型糖尿病患者亲属的糖尿病进展更密切相关的GAD自身抗体。

Reactivity to N-Terminally Truncated GAD65(96-585) Identifies GAD Autoantibodies That Are More Closely Associated With Diabetes Progression in Relatives of Patients With Type 1 Diabetes.

作者信息

Williams Alistair J K, Lampasona Vito, Wyatt Rebecca, Brigatti Cristina, Gillespie Kathleen M, Bingley Polly J, Achenbach Peter

机构信息

School of Clinical Sciences, University of Bristol, Bristol, U.K.

Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy.

出版信息

Diabetes. 2015 Sep;64(9):3247-52. doi: 10.2337/db14-1694. Epub 2015 May 22.

Abstract

GAD autoantibodies (GADAs) identify individuals at increased risk of developing type 1 diabetes, but many people currently found to be GADA positive are unlikely to progress to clinical disease. More specific GADA assays are therefore needed. Recent international workshops have shown that the reactivity of sera from healthy donors varies according to assay type and indicated that the use of N-terminally truncated GAD65 radiolabels in GADA radiobinding assays is associated with higher specificity. To determine whether a radiobinding assay using radiolabeled GAD65(96-585) identified individuals who are at higher risk of developing diabetes, samples from recent-onset patients and GADA-positive first-degree relatives participating in the Bart's-Oxford type 1 diabetes family study were reassayed with full-length or N-terminally truncated GAD using the National Institute of Diabetes and Digestive and Kidney Diseases harmonized protocol. The sensitivity in patients was the same with both labels, but fewer relatives retested positive with truncated GAD. Among relatives who progressed to diabetes, similar proportions were found to be GADA positive when tested with either label, but because of their higher specificity the cumulative risk of diabetes was higher in those with autoantibodies to GAD65(96-585). Autoantibodies to GAD65(96-585) in relatives are more closely associated with diabetes risk than those to full-length GAD, suggesting that assays using N-terminally truncated GAD should be used to select participants for intervention trials.

摘要

谷氨酸脱羧酶自身抗体(GADA)可识别出1型糖尿病发病风险增加的个体,但目前发现许多GADA呈阳性的人不太可能发展为临床疾病。因此,需要更具特异性的GADA检测方法。最近的国际研讨会表明,健康供者血清的反应性因检测方法类型而异,并指出在GADA放射结合试验中使用N端截短的GAD65放射性标记物具有更高的特异性。为了确定使用放射性标记的GAD65(96-585)进行的放射结合试验能否识别出糖尿病发病风险较高的个体,我们采用美国国立糖尿病、消化和肾脏疾病研究所的统一方案,使用全长或N端截短的GAD对参与巴茨-牛津1型糖尿病家族研究的近期发病患者和GADA阳性的一级亲属的样本进行了重新检测。两种标记物对患者的检测灵敏度相同,但使用截短GAD重新检测时,亲属中呈阳性的人数较少。在进展为糖尿病的亲属中,使用两种标记物检测时发现GADA呈阳性的比例相似,但由于其更高的特异性,针对GAD65(96-585)产生自身抗体的亲属患糖尿病的累积风险更高。亲属中针对GAD65(96-585)的自身抗体比针对全长GAD的自身抗体与糖尿病风险的关联更密切,这表明应使用采用N端截短GAD的检测方法来选择参与干预试验的受试者。

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