Institute for Experimental Endocrinology, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany.
Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, 13353 Berlin, Germany.
Int J Mol Sci. 2021 Dec 3;22(23):13088. doi: 10.3390/ijms222313088.
The essential trace element selenium (Se) is needed for the biosynthesis of selenocysteine-containing selenoproteins, including the secreted enzyme glutathione peroxidase 3 (GPX3) and the Se-transporter selenoprotein P (SELENOP). Both are found in blood and thyroid colloid, where they serve protective functions. Serum SELENOP derives mainly from hepatocytes, whereas the kidney contributes most serum GPX3. Studies using transgenic mice indicated that renal GPX3 biosynthesis depends on Se supply by hepatic SELENOP, which is produced in protein variants with varying Se contents. Low Se status is an established risk factor for autoimmune thyroid disease, and thyroid autoimmunity generates novel autoantigens. We hypothesized that natural autoantibodies to SELENOP are prevalent in thyroid patients, impair Se transport, and negatively affect GPX3 biosynthesis. Using a newly established quantitative immunoassay, SELENOP autoantibodies were particularly prevalent in Hashimoto's thyroiditis as compared with healthy control subjects (6.6% versus 0.3%). Serum samples rich in SELENOP autoantibodies displayed relatively high total Se and SELENOP concentrations in comparison with autoantibody-negative samples ([Se]; 85.3 vs. 77.1 µg/L, = 0.0178, and [SELENOP]; 5.1 vs. 3.5 mg/L, = 0.001), while GPX3 activity was low and correlated inversely to SELENOP autoantibody concentrations. In renal cells in culture, antibodies to SELENOP inhibited Se uptake. Our results indicate an impairment of SELENOP-dependent Se transport by natural SELENOP autoantibodies, suggesting that the characterization of health risk from Se deficiency may need to include autoimmunity to SELENOP as additional biomarker of Se status.
必需微量元素硒（Se）是合成含硒半胱氨酸的硒蛋白所必需的，包括分泌酶谷胱甘肽过氧化物酶 3（GPX3）和硒转运蛋白硒蛋白 P（SELENOP）。这两种物质都存在于血液和甲状腺胶体中，发挥着保护作用。血清 SELENOP 主要来源于肝细胞，而肾脏对血清 GPX3 的贡献最大。使用转基因小鼠的研究表明，肾脏 GPX3 的生物合成依赖于肝脏 SELENOP 提供的硒供应，而 SELENOP 是由具有不同硒含量的蛋白质变异体产生的。低硒状态是自身免疫性甲状腺疾病的一个既定危险因素，而甲状腺自身免疫会产生新的自身抗原。我们假设，甲状腺患者中存在针对 SELENOP 的天然自身抗体，这些自身抗体可损害硒的运输，并对 GPX3 的生物合成产生负面影响。使用新建立的定量免疫分析法，与健康对照组相比，桥本甲状腺炎患者的 SELENOP 自身抗体更为常见（6.6%对 0.3%）。与自身抗体阴性样本相比，富含 SELENOP 自身抗体的血清样本的总硒和 SELENOP 浓度相对较高（[Se]：85.3 对 77.1 µg/L， = 0.0178，和 [SELENOP]：5.1 对 3.5 mg/L， = 0.001），而 GPX3 活性较低，并与 SELENOP 自身抗体浓度呈负相关。在体外培养的肾细胞中，针对 SELENOP 的抗体抑制了硒的摄取。我们的研究结果表明，天然 SELENOP 自身抗体可损害 SELENOP 依赖性硒运输，表明硒缺乏的健康风险评估可能需要将针对 SELENOP 的自身免疫作为硒状态的附加生物标志物。
Zotero 插件
