Department of Analytical Chemistry, Ghent University, Krijgslaan 281-S12, BE-9000 Ghent, Belgium.
Metallomics. 2013 Nov;5(11):1503-9. doi: 10.1039/c3mt00054k.
As the iron status of an individual cannot be adequately assessed on the basis of the (total) Fe concentration in whole blood or serum, in medicine a number of parameters, such as the serum concentrations of ferritin, transferrin and soluble transferrin receptor and the transferrin saturation, are routinely determined instead. As previous research has shown that also the isotopic composition of Fe in blood and tissues is dependent on the metabolism, the present study assessed whether Fe isotopic composition in whole blood provides information as to an individual's iron status. Fe isotopic analysis of whole blood samples from a reference population (healthy volunteers) was carried out using multi-collector ICP-mass spectrometry (after chromatographic target element isolation) and the results obtained were investigated by statistical means as to their potential relation with the iron status parameters conventionally used in medicine. A low δ(56)Fe value was demonstrated to coincide with high iron status and a high δ(56)Fe value with low iron status, thus reflecting the response of the body to this iron status in terms of iron uptake, distribution between blood and stores and mobilization of storage iron. In a second phase, the iron isotopic composition in blood from patients treated for hemochromatosis type I and from patients with anemia of chronic disease (ACD) was determined. The results for hemochromatosis patients plotted with the values of low iron status, while those for ACD patients plotted with the values of high iron status. By taking a closer look at the aberrant iron metabolism that comes with these diseases, it can be seen that the patient samples confirm the conclusions drawn for the reference population. Patients with hemochromatosis type I have a strongly upregulated iron uptake, like healthy individuals with low iron status. The metabolism of patients suffering from ACD tries to remove iron from the circulation by downregulating the iron uptake, moving more absorbed iron to the stores and by not using any iron from these storage sites, which is in agreement with the responses of the human body to high iron status. This suggests that the conclusions made for healthy individuals are extendable to patients with aberrant iron metabolism.
由于个体的铁状态不能仅基于全血或血清中的(总)Fe 浓度来充分评估,因此在医学中通常会测定其他一些参数,如血清铁蛋白、转铁蛋白和可溶性转铁蛋白受体的浓度以及转铁蛋白饱和度。由于之前的研究表明血液和组织中的 Fe 同位素组成也依赖于新陈代谢,因此本研究评估了全血中的 Fe 同位素组成是否能提供个体铁状态的信息。采用多接收电感耦合等离子体质谱法(在色谱目标元素分离后)对参考人群(健康志愿者)的全血样本进行 Fe 同位素分析,并通过统计学方法研究其与医学中常规使用的铁状态参数之间的潜在关系。结果表明,低 δ(56)Fe 值与高铁状态相关,而高 δ(56)Fe 值与低铁状态相关,这反映了机体对铁摄取、血液和储存之间的分布以及储存铁动员的这种铁状态的反应。在第二阶段,测定了接受 I 型血色病治疗的患者和患有慢性病贫血(ACD)的患者的血液铁同位素组成。血色病患者的结果与低铁状态的值相关,而 ACD 患者的结果与高铁状态的值相关。通过更仔细地观察这些疾病所伴随的异常铁代谢,可以看出患者样本证实了针对参考人群得出的结论。I 型血色病患者的铁摄取明显上调,就像低铁状态的健康个体一样。患有 ACD 的患者的新陈代谢试图通过下调铁摄取、将更多吸收的铁转移到储存部位以及不使用这些储存部位的任何铁来从循环中去除铁,这与人体对高铁状态的反应一致。这表明针对健康个体得出的结论可扩展到铁代谢异常的患者。