Purpose

Advanced glycation end products (AGEs) are increased in conditions of oxidative stress and promote inflammation by interacting with their receptor RAGE on cell membrane. By contrast, the soluble receptor sRAGE exerts protective effects by competing with RAGE for ligand binding. AGEs/sRAGEs interaction is involved in the pathogenesis of several diseases related to oxidative stress. In the present study, we evaluated the AGEs/sRAGEs oxidative balance in Hashimoto’ thyroiditis (HT).

Methods

We measured the levels of sRAGE, by ELISA, and AGEs, by spectrophotometric method, in the serum of 50 HT patients (5 M, 45 F; mean age 38.5 ± 12 years) and 50 age-, sex- and BMI-matched healthy controls. All subjects were euthyroid at recruitment and none was on LT-4 therapy.

Results

Serum sRAGEs were significantly lower (median 424 vs 738 pg/ml; p = 0.001) and AGEs higher (205 vs 114 AU/g prot; p = 0.001) in HT patients compared to controls, and the two parameters were inversely correlated (p = 0.016). Accordingly, the AGEs/sRAGEs ratio was threefold higher in HT patients than controls (0.48 vs 0.15; p = 0.0001). In regression analysis models, serum TPO-Ab were the main predictors for AGEs and sRAGEs levels and AGEs/sRAGEs ratio (p < 0.0001), irrespective of TSH and/or FT4 values.

Conclusion

sRAGEs were decreased and AGEs increased, suggesting a dysregulation of AGE/sRAGEs-related oxidative homeostasis in HT patients, even when in euthyroid status. Autoimmunity per se seems to play an important role in AGEs/sRAGE imbalance, irrespective of thyroid function alterations.

中文翻译：

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在桥本甲状腺炎中，晚期糖基化终末产物（AGEs）的血清水平升高，而可溶性受体（sRAGE）降低。

目的

晚期糖基化终产物（AGEs）在氧化应激条件下会增加，并通过与其在细胞膜上的受体RAGE相互作用而促进炎症。相反，可溶性受体sRAGE通过与RAGE竞争配体结合而发挥保护作用。AGEs / sRAGEs相互作用参与了多种与氧化应激有关的疾病的发病机理。在本研究中，我们评估了桥本甲状腺炎（HT）中AGEs / sRAGEs的氧化平衡。

方法

我们通过ELISA和分光光度法测量了50例HT患者（5 M，45 F；平均年龄38.5±12岁）和50例年龄，性别和BMI匹配的健康者血清中的sRAGE水平和分光光度法控制。所有受试者在募集时甲状腺功能正常，均未接受LT-4治疗。

结果

 与对照组相比，HT患者的血清sRAGEs显着降低（中位数424 vs 738 pg / ml；p  = 0.001），而AGEs更高（205 vs 114 AU / g prot；p = 0.001），并且这两个参数呈负相关（p  = 0.016）。因此，HT患者的AGEs / sRAGEs比对照组高三倍（0.48 vs 0.15；p  = 0.0001）。在回归分析模型中， 无论TSH和/或FT4值如何，血清TPO-Ab都是AGEs和sRAGEs水平以及AGEs / sRAGEs比值的主要预测因子（p <0.0001）。

结论

sRAGEs降低而AGEs升高，这表明HT患者中AGE / sRAGEs相关的氧化稳态失调，即使处于甲状腺功能正常的状态。自身免疫似乎在AGEs / sRAGE失衡中起着重要作用，而与甲状腺功能改变无关。