Ganz Tomas, Jung Grace, Naeim Arash, Ginzburg Yelena, Pakbaz Zahra, Walter Patrick B, Kautz Léon, Nemeth Elizabeta
Department of Medicine and.
Department of Pathology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA.
Blood. 2017 Sep 7;130(10):1243-1246. doi: 10.1182/blood-2017-04-777987. Epub 2017 Jul 24.
Erythroferrone (ERFE) is a glycoprotein hormone secreted by erythroblasts in response to stimulation by erythropoietin (EPO). We previously demonstrated that ERFE messenger RNA expression and serum protein concentration increase in mice subjected to hemorrhage or EPO therapy, that ERFE acts on hepatocytes to suppress hepcidin, and that the resulting decrease in hepcidin augments iron delivery for intensified erythropoiesis. We also showed that ERFE contributes to pathological hepcidin suppression and iron overload in mice with nontransfused β-thalassemia. We now report the development and technical validation of a rabbit monoclonal antibody-based sandwich immunoassay for human ERFE. We use this assay to show that blood loss or EPO administration increases serum ERFE concentrations in humans, and that patients with both nontransfused and transfused β-thalassemia have very high serum ERFE levels, which decrease after blood transfusion. The assay should be useful for human studies of normal and disordered erythropoiesis and its effect on iron homeostasis.
促红细胞生成素铁蛋白（ERFE）是一种糖蛋白激素，由成红细胞在促红细胞生成素（EPO）刺激下分泌。我们之前证明，在遭受出血或接受EPO治疗的小鼠中，ERFE信使核糖核酸表达及血清蛋白浓度会升高，ERFE作用于肝细胞以抑制铁调素，而铁调素的减少会增加铁输送以强化红细胞生成。我们还表明，ERFE会导致未输血的β地中海贫血小鼠出现病理性铁调素抑制和铁过载。我们现在报告一种基于兔单克隆抗体的夹心免疫分析法用于检测人ERFE的开发及技术验证。我们使用该分析法表明，失血或给予EPO会增加人体血清ERFE浓度，并且未输血和输血后的β地中海贫血患者血清ERFE水平都非常高，输血后该水平会下降。该分析法应有助于对正常和紊乱的红细胞生成及其对铁稳态的影响进行人体研究。
