AIMS 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'. METHODS 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. KEYFINDINGS 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. SIGNIFICANCE 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.

中文翻译：

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甲基乙二醛 (MG) 糖化 LDL 上的新表位产生自身免疫反应；具有不同病程的 T2DM 患者的自身免疫检测。

目的 生物分子的非酶促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) 是一种高活性羰基化合物，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。糖基化还导致自由基的产生，引起结构扰动，从而导致在 LDL 分子上产生新抗原表位。本研究的目的是调查 LDL 的改变是否会导致 2 型糖尿病患者产生自身抗体。方法 与健康和年龄匹配的对照 (n = 50) 和疾病持续时间 (DD) 5-15 年 (n = 80) 和DD > 15 岁 (n = 50) 通过直接结合 ELISA 检查。关键发现 与其天然类似物相比，在 50% 的 DD 5-15 的 T2DM 和 62% 的 DD > 15 的 T2DM 患者中观察到高亲和力结合，与 MG-LDL 抗原的血清抗体相比（P < 0.05）。NHS 血清显示与天然和糖化 LDL 的结合可以忽略不计。竞争性抑制 ELISA 结果显示出比直接结合 ELISA 结果更高的亲和力血清 IgG。在 T2DM 患者的血清和 NHS 血清中也观察到糖化中间产物和终产物的增加。意义 LDL 大分子上可能会产生新抗原表位，导致 T2DM 中产生抗体。抗体的流行取决于疾病持续时间。