Antigenic role of the adaptive immune response to D-ribose glycated LDL in diabetes, atherosclerosis and diabetes atherosclerotic patients
Antigenic role of the adaptive immune response to D-ribose glycated LDL in diabetes, atherosclerosis and diabetes atherosclerotic patients
复制标题
糖尿病、动脉粥样硬化和糖尿病动脉粥样硬化患者对 D-核糖糖化低密度脂蛋白的适应性免疫反应的抗原作用
DOI：
10.1016/j.lfs.2016.02.013
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发表时间：
2016-04-15
期刊：
影响因子：
6.1
通讯作者：
Ahmad, Saheem
中科院分区：
文献类型：
--
作者：
Akhter, Firoz;Khan, M. Salman;Ahmad, Saheem
目的：蛋白质糖基化导致晚期糖基化终产物（age）的形成，AGEs在糖尿病并发症的病理生理中具有重要作用。d -核糖似乎是天然存在的糖中活性最强的，对AGEs的产生有重要贡献。糖基化还导致自由基的产生，导致结构修饰，从而导致新抗原表位的产生。本研究的目的是研究LDL修饰是否会导致糖尿病和动脉粥样硬化患者形成针对其糖化构象的自身抗体。方法：评估患者循环自身抗体对天然LDL和修饰LDL的结合特性。采用直接结合ELISA和抑制ELISA检测T2D（105例）、ATH（106例）和T2D-ATH患者（72例），并与年龄匹配的健康对照组（50例）进行比较。此外，还对这些患者和健康受试者的酮胺部分、HMF和羰基含量进行了估计。重点发现：41.91%的T2D、54.72%的ATH和70.83%的T2D-ATH患者血清对d -核糖糖化LDL的特异性结合程度高于其天然类似物（P < 0.05）。正常人血清与这两种抗原的结合可忽略不计。竞争性抑制ELISA法重申了直接结合的结果。患者血清中HMF、酮胺和羰基含量均高于健康人。意义：LDL糖化导致结构扰动，导致新抗原表位的产生，这些表位是T2D、ATH和T2D-ATH患者抗体的更好抗原，其中T2D-ATH患者对核糖化LDL的自身抗体的患病率更高。(C) 2016 Elsevier Inc.版权所有。
Aims: Glycation of proteins leads to the formation of advanced glycation end products (AGEs, which have significant role in the pathophysiology of diabetes complications. D-ribose appears to be the most reactive among the naturally occurring sugars and contribute significantly to the generation of AGEs. Glycation also results in the generation of free radicals causing structural modification which leads to the generation of neoantigenic epitopes. The aim of the present study was to investigate whether LDL modification results in auto-antibodies formation against its glycated conformer in diabetes and atherosclerosis patients.Methods: The binding characteristics of circulating auto-antibodies in patients against native and modified LDL were assessed. T2D (n = 105), ATH (n = 106) and T2D-ATH patients (n = 72) were examined by direct binding ELISA as well as inhibition ELISA, compared with healthy age-matched controls (n = 50). Furthermore, ketoamine moieties, HMF and carbonyl content were also estimated in these patient's and healthy subjects.Key findings: High degree of specific binding was observed by 41.91% of T2D, 54.72% of ATH and 70.83% T2D-ATH patient's sera towards D-ribose glycated LDL, in comparison to its native analog (P < 0.05). Normal human sera showed negligible binding with either antigen. Competitive inhibition ELISA reiterates the direct binding results. The higher concentration of HMF, ketoamine and carbonyl content was observed in patient's sera than healthy subjects.Significance: LDL glycation results in structural perturbation causing generation of neoantigenic epitopes that are better antigens for antibodies in T2D, ATH and T2D-ATH patients where T2D-ATH subjects showed higher prevalence in auto-antibodies against ribosylated LDL. (C) 2016 Elsevier Inc. All rights reserved.