IIRC-1, Laboratory of Glycation Biology and Metabolic Disorders, Integral University, Lucknow, India; Department of Biosciences, Integral University, Lucknow, India.
Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, University of Hail, Hail, Saudi Arabia.
Cell Immunol. 2020 May;351:104062. doi: 10.1016/j.cellimm.2020.104062. Epub 2020 Feb 7.
Non-enzymatic reaction of biomolecules leads to the formation of advanced glycation end products (AGEs). AGEs plays significant role in the pathophysiology of type 2 diabetes mellitus. Methylglyoxal (MG) is a highly reactive carbonyl compound which causes formation of early (ketoamines), intermediate (dicarbonyls) and advanced glycation end products (AGEs). Glycation also results in the generation of free radicals causing structural perturbations which leads to the generation of neoantigenic epitopes on LDL molecules. The aim of the present study was to investigate whether the modification of LDL results in auto-antibodies generation in type 2 diabetes patients'.
The binding affinity of circulating autoantibodies in patients against native and MG modified LDL were assessed as compared with healthy and age-matched controls (n = 50) and T2DM patients with disease duration (DD) 5-15 yrs (n = 80) and DD > 15 yrs (n = 50) were examined by direct binding ELISA.
The high affinity binding were observed in 50% of T2DM with DD 5-15 and 62% of T2DM with DD > 15 of patient's sera antibodies to MG-LDL antigen, in comparison to its native analog (P < 0.05). NHS sera showed negligible binding with both native and glycated LDL. Competitive inhibition ELISA results exhibit greater affinity sera IgG than the direct binding ELISA results. The increase in glycation intermediate and ends product were also observed in T2DM patient's sera and NHS sera.
There might be the generation of neoantigenic epitopes on LDL macromoleucle which results in generation of antibodies in T2DM. The prevalence of antibodies was dependent on disease duration.
生物分子的非酶反应导致晚期糖基化终产物（AGEs）的形成。AGEs 在 2 型糖尿病的病理生理学中起重要作用。甲基乙二醛（MG）是一种高度反应性的羰基化合物，可导致早期（酮胺）、中间（二羰基）和晚期糖基化终产物（AGEs）的形成。糖化还会导致自由基的产生，从而导致结构扰动，导致 LDL 分子上新的抗原表位的产生。本研究旨在探讨 LDL 的修饰是否会导致 2 型糖尿病患者产生自身抗体。
评估患者循环自身抗体与天然和 MG 修饰的 LDL 的结合亲和力，并与健康和年龄匹配的对照（n=50）进行比较，同时还检查了病程（DD）为 5-15 年（n=80）和 DD>15 年（n=50）的 T2DM 患者的直接结合 ELISA。
与天然类似物相比，5-15 年 DD 的 T2DM 患者中有 50%，DD>15 年的 T2DM 患者中有 62%的血清抗体对 MG-LDL 抗原具有高亲和力结合（P<0.05）。NHS 血清对天然和糖化 LDL 的结合可忽略不计。竞争性抑制 ELISA 结果显示，血清 IgG 的亲和力大于直接结合 ELISA 结果。还观察到 T2DM 患者血清和 NHS 血清中糖基化中间产物和末端产物的增加。
LDL 大分子上可能会产生新的抗原表位，导致 T2DM 产生抗体。抗体的出现与疾病持续时间有关。
