A specific and sensitive assay for blood levels of glycated CD59: a novel biomarker for diabetes.
A specific and sensitive assay for blood levels of glycated CD59: a novel biomarker for diabetes.
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DOI：
10.1002/ajh.23478
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发表时间：
2013-08
影响因子：
12.8
通讯作者：
Halperin, Jose A.
中科院分区：
文献类型：
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作者：
Ghosh, Pamela;Sahoo, Rupam;Vaidya, Anand;Cantel, Sonia;Kavishwar, Amol;Goldfine, Allison;Herring, Neil;Bry, Lynn;Chorev, Michael;Halperin, Jose A.
越来越多的证据将补体系统与人类糖尿病并发症联系起来。补体调节蛋白CD 59是一种膜攻击复合物（MAC）形成的抑制剂，可被高血糖诱导的糖基化抑制，从而促进MAC沉积增加，MAC是补体介导的组织损伤的主要效应物。CD 59是一种普遍存在的GPI锚定膜蛋白，通过磷脂酶从细胞膜脱落，产生存在于血液和尿液中的可溶性形式。我们建立了一种ELISA来测量血清/血浆糖化hCD 59（GCD 59），并评估其作为糖尿病生物标志物的潜力。我们使用合成肽策略生成a）捕获hCD 59的小鼠单克隆抗体，B）检测GCD 59的兔单克隆抗体，以及c）用于测定标准化的GCD 59替代物。ELISA条件进行了优化的精密度，重现性和临床灵敏度。最初在24名患有或不患有糖尿病的受试者中评价了该测定的临床效用，并在一项包括100名患有糖尿病的受试者和90名未诊断为糖尿病的受试者的研究中进一步验证。GCD 59 a）在糖尿病患者中显著高于非糖尿病患者，B）与HbA 1c独立相关，和）以高特异性和敏感性识别糖尿病患者。我们报告的发展和标准化的一种新的，敏感的，和具体的ELISA测量GCD 59在血液中。该检测区分了糖尿病患者和非糖尿病患者，并显示GCD 59和HbA 1c之间存在很强的相关性。由于GCD 59可能有助于糖尿病并发症的发病机制，因此测量GCD 59的血液水平可能有助于糖尿病的诊断和管理。
Increasing evidence links the complement system with complications of human diabetes. The complement regulatory protein CD59, an inhibitor of formation of membrane attack complex (MAC), is inhibited by hyperglycemia-induced glycation fostering increased deposition of MAC, a major effector of complement-mediated tissue damage. CD59, an ubiquitous GPI-anchored membrane protein, is shed from cell membranes by phospholipases generating a soluble form present in blood and urine. We established an ELISA to measure serum/plasma glycated hCD59 (GCD59) and evaluated its potential as a diabetes biomarker. We used a synthetic peptide strategy to generate a) a mouse monoclonal antibody to capture hCD59, b) a rabbit monoclonal antibody to detect GCD59, and c) a GCD59 surrogate for assay standardization. ELISA conditions were optimized for precision, reproducibility and clinical sensitivity. The clinical utility of the assay was initially evaluated in 24 subjects with or without diabetes and further validated in a study that included 100 subjects with and 90 subjects without a diagnosis of diabetes. GCD59 a) was significantly higher in individuals with than in individual without diabetes, b) was independently associated with HbA1c, and) identified individuals with diabetes with high specificity and sensitivity. We report the development and standardization of a novel, sensitive, and specific ELISA for measuring GCD59 in blood. The assay distinguished individuals with diabetes from those without, and showed strong correlation between GCD59 and HbA1c. Because GCD59 likely contributes to the pathogenesis of diabetes complications, measurement of blood levels of GCD59 may be useful in the diagnosis and management of diabetes.
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影响因子：
4.3
作者：
Johansen, Morten Bo;Kiemer, Lars;Brunak, Soren
通讯作者：
Brunak, Soren
影响因子：
5.7
作者：
Acosta, JA;Benzaquen, LR;Halperin, JA
通讯作者：
Halperin, JA
影响因子：
7.7
作者：
Qin, XB;Goldfine, A;Halperin, JA
通讯作者：
Halperin, JA
影响因子：
11.2
作者：
Perk, Jonathan;Gil-Bazo, Ignacio;Benezra, Robert
通讯作者：
Benezra, Robert
DOI：
10.1007/978-0-387-73657-0_141
发表时间：
2009-01-01
期刊：
PEPTIDES FOR YOUTH
影响因子：
--
作者：
Cantel, S.;Kavishwar, A.;Chorev, M.
通讯作者：
Chorev, M.