糖尿病及其并发症中血清抗体对晚期糖基化终产物的优先识别与低度全身炎症。
Preferential recognition of advanced glycation end products by serum antibodies and low-grade systemic inflammation in diabetes mellitus and its complications.
机构信息
Rajiv Gandhi Centre for Diabetes and Endocrinology, J.N. Medical College, Aligarh Muslim University, Aligarh 202002, India.
Rajiv Gandhi Centre for Diabetes and Endocrinology, J.N. Medical College, Aligarh Muslim University, Aligarh 202002, India.
出版信息
Int J Biol Macromol. 2018 Oct 15;118(Pt B):1884-1891. doi: 10.1016/j.ijbiomac.2018.07.033. Epub 2018 Jul 17.
BACKGROUND
Advanced glycation end products (AGEs) have shown to possess antigenicity. This study analyzes the detrimental effect of non-enzymatic glycation on human serum albumin (HSA) leading to the production of antibodies.
METHODS
HSA (20 μM) incubated with d-glucose formed AGEs confirmed by scanning electron microscopy (SEM). DNA-damage was assessed with comet assay. Antibodies against in-vitro formed AGEs was evaluated in the sera of diabetic patients by enzyme-linked immunosorbent assay. Molecular docking was performed to demonstrate affinity of native and glycated-HSA with IgG. Low-grade systemic inflammation was quantified with IL-4, IL-6, TNF-α and NF-кβ in serum and mRNA expression.
RESULTS
Scanning Electron Microscopy showed the formation of aggregates in glycated-HSA. Comet assay showed DNA damage T2DM with CKD. Serum auto-antibodies in diabetes patients with chronic kidney disease (CKD) showed appreciably high recognition with glycated-HSA compared to native HSA. Molecular docking showed less affinity of glycated-HSA with IgG. Serum IL-4, IL-6, and TNF-α were found significantly higher in T2DM with CKD compared to T2DM and healthy ones. mRNA expression of IL-4, IL-6 and NF-кβ are also found significantly higher in T2DM with CKD.
CONCLUSION
The non-enzymatic glycation-induced damage to the HSA generate neo-epitopes that possess immunogenic response and low-grade systemic inflammation.
背景
晚期糖基化终产物（AGEs）已显示出抗原性。本研究分析了非酶糖基化对人血清白蛋白（HSA）的有害影响，导致产生抗体。
方法
用 d-葡萄糖孵育 20 μM 的 HSA 形成 AGEs，通过扫描电子显微镜（SEM）确认。通过彗星试验评估 DNA 损伤。通过酶联免疫吸附试验评估糖尿病患者血清中针对体外形成的 AGEs 的抗体。进行分子对接以证明天然和糖基化-HSA 与 IgG 的亲和力。通过 IL-4、IL-6、TNF-α 和 NF-кβ 在血清和 mRNA 表达中定量低水平全身性炎症。
结果
扫描电子显微镜显示糖基化-HSA 形成了聚集体。彗星试验显示 DNA 损伤。糖尿病伴慢性肾脏病（CKD）患者的血清自身抗体对糖基化-HSA 的识别明显高于天然 HSA。分子对接显示糖基化-HSA 与 IgG 的亲和力降低。与 T2DM 和健康对照组相比，T2DM 伴 CKD 患者的血清 IL-4、IL-6 和 TNF-α 明显升高。IL-4、IL-6 和 NF-кβ 的 mRNA 表达也在 T2DM 伴 CKD 中明显升高。
结论
HSA 的非酶糖基化诱导损伤产生新表位，具有免疫原性反应和低水平全身性炎症。
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