Department of Medicine, University of Louisville, Louisville, Kentucky, USA.
The Robley Rex Veterans Affairs Medical Center, Louisville, Kentucky, USA.
Kidney Int. 2011 Mar;79(5):546-554. doi: 10.1038/ki.2010.468. Epub 2010 Dec 8.
Biomarkers that evaluate the response to erythropoietic-stimulating agents largely measure inflammation and iron availability. While these are important factors in modifying an individual's response to these agents, they do not address all aspects of a poor response. To clarify this, we isolated peptides in the serum of good and poor responders to erythropoietin in order to identify biomarkers of stimulating agent response. Ninety-one candidate biomarker targets were identified and characterized using mass spectrometry, of which tandem mass spectroscopy provided partial amino-acid sequence information of 17 different peptides for 16 peptide masses whose abundance significantly differed between poor and good responders. The analysis concluded that three peptides associated with a poor response were derived from oncostatin M receptor β (OSMRβ). The 13 serum peptides associated with a good response were derived from fibrinogen α and β, coagulation factor XIII, complement C3, and cysteine/histidine rich 1(CYHR1). Poor response was most strongly associated with the OSMRβ fragment with the largest molecular weight, while a good response was most strongly associated with CYHR1. Immunoblots found the abundance of intact OSMRβ and CYHR1 significantly differed between good and poor responders. Thus, two measurable biomarkers of the response to erythropoietic-stimulating agents are present in the serum of treated patients.
生物标志物可评估促红细胞生成刺激剂的反应,主要用于测量炎症和铁的可利用性。虽然这些是改变个体对这些药物反应的重要因素,但它们并不能解决反应不佳的所有方面。为了阐明这一点,我们从促红细胞生成素的良好和不良反应者的血清中分离出肽,以确定刺激剂反应的生物标志物。使用质谱法鉴定了 91 种候选生物标志物靶标,并对其进行了表征,其中串联质谱法为 16 个肽质量提供了 17 个不同肽的部分氨基酸序列信息,这些肽质量在不良和良好反应者之间的丰度存在显著差异。分析结果表明,与不良反应相关的三种肽来自于肿瘤坏死因子受体 β(OSMRβ)。与良好反应相关的 13 种血清肽来自纤维蛋白原 α 和 β、凝血因子 XIII、补体 C3 和富含半胱氨酸/组氨酸的 1(CYHR1)。不良反应与分子量最大的 OSMRβ 片段关系最密切,而良好反应与 CYHR1 关系最密切。免疫印迹发现完整的 OSMRβ 和 CYHR1 在良好和不良反应者之间的丰度存在显著差异。因此,促红细胞生成刺激剂反应的两种可测量生物标志物存在于接受治疗的患者的血清中。