High-throughput multiplexed autoantibody detection to screen type 1 diabetes and multiple autoimmune diseases simultaneously

High-throughput multiplexed autoantibody detection to screen type 1 diabetes and multiple autoimmune diseases simultaneously
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高通量多重自身抗体检测同时筛查1型糖尿病和多种自身免疫性疾病

DOI:
10.1016/j.ebiom.2019.08.036
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发表时间:
2019-09-01
期刊:
影响因子:
11.1
通讯作者:
Yu, Liping
Yu, Liping
中科院分区:
医学1区
文献类型:
--
作者:
Gu, Yong;Zhao, Zhiyuan;Yu, Liping

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背景:胰岛自身抗体(IAb)是评估临床1型糖尿病(T1 D)进展风险的最可靠生物标志物。目前在临床试验中使用的四种主要的生化定义的IAb对疾病预测同样重要。目前的IAb筛选方法采用放射结合法(Radio-binding assay,RBA)进行单克隆抗体的检测,这对于大规模的IAb筛选来说是费力且低效的。更重要的是,高达40%的T1 D患者有其他自身免疫性疾病,可以通过相关的自身抗体检测来识别。因此,需要同时筛查T1 D和其他自身免疫性疾病。方法:基于我们完善的电化学发光(ECL)测定平台,我们开发了一种多重ECL测定,其在一个单一孔中将7种单独的自身抗体测定组合在一起,以同时筛查T1 D和其他三种自身免疫性疾病,包括乳糜泻,自身免疫性甲状腺疾病和自身免疫性多腺体综合征-1(APS-1)。7-β ECL检测针对单抗体测量进行了广泛验证,包括标准RBA和单ECL检测。结果:7-β ECL检测与每个单ECL自身抗体检测和每个RBA都有良好的相关性。解释:多重ECL测定提供高灵敏度和疾病特异性,沿着高通量和低成本,用于在普通人群中大规模筛查T1 D和其他相关自身免疫疾病。(C)2019作者由爱思唯尔公司出版
Background: Islet autoantibodies (IAbs) are the most reliable biomarkers to assess risk of progression to clinical type 1 diabetes (T1D). There are four major biochemically defined IAbs currently used in clinical trials that are equally important for disease prediction. The current screening methods use a radio-binding assay (RBA) for single IAb measurement, which are laborious and inefficient for large-scale screening. More importantly, up to 40% of patients with T1D have other autoimmune conditions that can be identified through relevant autoantibody testing. Thus, there is a need to screen for T1D and other autoimmune diseases simultaneously.Methods: Based on our well-established electrochemiluminescence (ECL) assay platform, we developed a multiplexed ECL assay that combines 7 individual autoantibody assays together in one single well to simultaneously screen T1D, and three other autoimmune diseases including celiac disease, autoimmune thyroid disease and autoimmune poly-glandular syndrome-1 (APS-1). The 7-Plex ECL assay was extensively validated against single antibody measurements including a standard RBA and single ECL assay.Findings: The 7-Plex ECL assay was well correlated to each single ECL autoantibody assay and each RBA.Interpretation: The multiplexed ECL assay provides high sensitivity and disease specificity, along with high throughput and a low cost for large-scale screenings of T1D and other relevant autoimmune diseases in the general population. (C) 2019 The Authors. Published by Elsevier B.V.