转铁蛋白受体2研究进展

转铁蛋白受体 2(transferrin receptor 2,TfR2)是一种新近发现的铁转运和铁稳态调节蛋白,在基因结构、蛋白结构、与转铁蛋白(Tf)结合和铁摄取方面与转铁蛋白受体 1(transferrin receptor 1,TfR1)具有相似性,但在mRNA表达的组织分布和调节方面有很大的差异。TfR2 mRNA不具有3’-端未翻译区的铁效应元件(Iron Responsive Element,IRE)结构,其表达水平不受细胞内铁状况的调节,在肝细胞、红系前体细胞、K562细胞和HepG2细胞高水平表达。TfR2的突变可导致遗传性血色病Ⅲ的发生。TfR2可能在铁转运、铁代谢调节、肝脏功能和红系细胞分化发育方面具有十分重要的作用,可能是红系前体细胞的一种分子标志。现综述TfR2基因和蛋白的结构特点、mRNA的表达和调控,及其可能的生物学功能。     

转铁蛋白受体2研究进展

转铁蛋白受体2(transferrin receptor2，TfR2)是一种新近发现的铁转运和铁稳态调节蛋白，在基因结构、蛋白结构、与转铁蛋白(Tf)结合和铁摄取方面与转铁蛋白受体1(transferrin receptorl，TfRl)具有相似性，但在mRNA表达的组织分布和调节方面有很大的差异。TfR2 mRNA不具有3’一端未翻译区的铁效应元件(Iron Responsive Element，IRE)结构，其表达水平不受细胞内铁状况的调节，在肝细胞、红系前体细胞、K562细胞和HepG2细胞高水平表达。TfR2的突变可导致遗传性血色病Ⅲ的发生。TfR2可能在铁转运、铁代谢调节、肝脏功能和红系细胞分化发育方面具有十分重要的作用，可能是红系前体细胞的一种分子标志。现综述TfR2基因和蛋白的结构特点、mRNA的表达和调控，及其可能的生物学功能。     

可溶性转铁蛋白受体评价骨髓造血的研究进展

转铁蛋白受体(TfR)在调节细胞铁摄取和维持机体铁稳态过程中发挥重要作用,主要表达于各阶段骨髓幼红细胞膜表面.可溶性转铁蛋白受体(sTfR)是膜表面受体的酶切形式,其血清水平除受机体铁贮存影响外,还与骨髓红系造血旺盛程度明显相关.现就sTfR作为反映骨髓红系细胞造血旺盛程度参数研究综述如下.     

转铁蛋白受体mRNA在MEL细胞中表达的调节

转铁蛋白受体(TfR)的主要功能是调节细胞的铁摄取量。它的表达除受细胞内铁含量影响外,在红系细胞还与血红素的合成和细胞的增殖状态有关,但在非红系细胞,则仅与细胞的增殖状态相关。本实验通过对小鼠红白血病(MEL)细胞在二甲基亚砜(DMSO)诱导分化前后、不同的铁状态和不同的血红素合成条件下,采用Northern印迹方法,观察TfR mRNA含量的变化。结果为:①在未诱导的MEL细胞,随着细胞的增殖,TfR mRNA含量增加;诱导的MEL细胞,虽然随着细胞分化成熟而丧失增殖能力,但当存在血红素合成时,TfR mRNA含量也增高,且增高幅度较非诱导组高。②在未诱导的MEL细胞,降低细胞内铁含量(培养液中加入去铁胺式抗TfR单克隆抗体),可刺激TfR mRNA表达;增加细胞内铁含量(培养液中加入转铁蛋白),则抑制TfR mRNA的表达;在诱导的MEL细胞,采用相同条件的铁状态时,细胞内TfR mRNA水平发生类似的改变,但变化的程度较小。③在未诱导的MEL细胞,加入血红素合成抑制剂(培养液中加入异烟肼),不改变TfR mRNA的表达;在诱导的MEL细胞,血红素合成抑制剂既抑制红系细胞的分化,也抑制TfR mRNA的表达。④当培养液中加入EPO,则促进诱导的MEL细胞内TfR mRNA的表达。上述结果提示,在红系细胞,TfR mRNA的表达除受细胞内铁调节外,也受细胞内血红素合成的     

肝转铁蛋白受体的结构、基因、表达与调控

转铁蛋白受体（TfR）是铁代谢的重要蛋白，由2个分子量为90kbDa的亚基以二硫键相连而成，其基因位于第三号染色体长臂，共有18个内含子和19个外显子，其cDNA为4．9kb，TfR在缺铁及细胞增殖时表达增多，而铁过剩时几乎不表达，其表达的调控在mRNA稳定性水平由铁来调节。     

转铁蛋白和转铁蛋白受体的研究进展

近年来发现转铁蛋白及其受体除运输铁的功能外,还与细胞生长和增殖有关。肿瘤细胞的转铁蛋白受体含量显著高于其相应正常细胞。本文从转铁蛋白和转铁蛋白受体的生物学特性及检测的临床意义几个方面刊物了综述。     

转铁蛋白和转铁蛋白受体的研究进展

近年来发现转铁蛋白及其受体除运输铁的功能外,还与细胞生长和增殖有关。肿瘤细胞的转铁蛋白受体含量显著高于其相应正常细胞。本文从转铁蛋白和转铁蛋白受体的生物学特性及检测的临床意义几方面进行了综述。     

转铁蛋白受体的结构、表达及功能

转铁蛋白受体（CD71）是参与铁的吸收和调节细胞生长的必需的蛋白。TfR敲除的胚胎在胚胎期的前12.5天内因为红细胞生成不足和神经发育不全而死亡。铁的运输是由Tf完成的，而它的吸收是通过TfR介导的内化过程实现的。TfR是一种Ⅱ型跨膜糖蛋白，是由两个同源二聚体（180 kDa）的亚基通过两条二硫键交联而成。     

慢性肾脏病晚期肾性贫血患者可溶性转铁蛋白受体水平变化及意义

目的探讨血清可溶性转铁蛋白受体（solubletransferrinreceptor,s—TfR）水平在慢性肾脏病（chronickidneydisease,CKD）晚期肾性贫血患者中的临床意义。方法CKD4～5期患者60例,测定血清s—TfR、铁蛋白、铁、转铁蛋白等指标水平,计算肾小球滤过率和转铁蛋白饱和度,比较CKD4期与5期患者铁状态评估指标的差异,分析s—TfR与铁蛋白及转铁蛋白饱和度的相关性。结果CKD4期患者铁蛋白、转铁蛋白饱和度明显高于5期患者,而s—TfR明显低于5期患者（P均〈0．05）;s—TfR与铁蛋白及转铁蛋白饱和度呈负相关（r=-0．398,P〈0．05;r=-0．817,P〈0．01）。结论CKD5期患者铁缺乏状态较CKD4期患者严重,s—TfR可作为判断CKD晚期肾性贫血患者体内铁缺乏的指标之     

转铁蛋白受体在血液系统恶性肿瘤治疗中的研究进展

铁是细胞生长增殖和机能活动所必需的元素之一。绝大多数细胞包括肿瘤细胞在内摄取铁主要通过转铁蛋白受体(transferrin receptor,TfR)介导。研究显示,转铁蛋白受体在肿瘤细胞表面高表达,因而可与多种物质联合应用于恶性肿瘤的治疗。本文从转铁蛋白受体结合药物(青蒿素、多柔比星和藤黄酸等)、基因、抗体、聚乙二醇、纳米方面对近年来转铁蛋白受体在血液系统恶性肿瘤治疗方面的研究进展进行了综述。     

Soluble transferrin receptor for the evaluation of erythropoiesis and iron status

Iron transport in the plasma is carried out by transferrin, which donates iron to cells through its interaction with a specific membrane receptor, the transferrin receptor (TfR). A soluble form of the TfR (sTfR) has been identified in animal and human serum. Soluble TfR is a truncated monomer of tissue receptor, lacking its first 100 amino acids, which circulates in the form of a complex of transferrin and its receptor. The erythroblasts rather than reticulocytes are the main source of serum sTfR. Serum sTfR levels average 5.0+/-1.0 mg/l in normal subjects but the various commercial assays give disparate values because of the lack of an international standard. The most important determinant of sTfR levels appears to be marrow erythropoietic activity which can cause variations up to 8 times below and up to 20 times above average normal values. Soluble TfR levels are decreased in situations characterized by diminished erythropoietic activity, and are increased when erythropoiesis is stimulated by hemolysis or ineffective erythropoiesis. Measurements of sTfR are very helpful to investigate the pathophysiology of anemia, quantitatively evaluating the absolute rate of erythropoiesis and the adequacy of marrow proliferative capacity for any given degree of anemia, and to monitor the erythropoietic response to various forms of therapy, in particular allowing to predict response early when changes in hemoglobin are not yet apparent. Iron status also influences sTfR levels, which are considerably elevated in iron deficiency anemia but remain normal in the anemia of inflammation, and thus may be of considerable help in the differential diagnosis of microcytic anemia. This is particularly useful to identify concomitant iron deficiency in a patient with inflammation because ferritin values are then generally normal. Elevated sTfR levels are also the characteristic feature of functional iron deficiency, a situation defined by tissue iron deficiency despite adequate iron stores. The sTfR/ferritin ratio can thus describe iron availability over a wide range of iron stores. With the exception of chronic lymphocytic leukemia (CLL) and high-grade non-Hodgkin's lymphoma and possibly hepatocellular carcinoma, sTfR levels are not increased in patients with malignancies. We conclude that soluble TfR represents a valuable quantitative assay of marrow erythropoietic activity as well as a marker of tissue iron deficiency.     

Biological and clinical aspects of soluble transferrin receptor

Soluble transferrin receptor (sTfR), one of the main regulators of cellular iron homeostasis, is the truncated form of the tissue receptor that is encoded by the human TfR gene (chromosome 3). Serum sTfR levels are determined to detect iron deficiency (ID) in inflammatory states and in anemia of chronic disease (ACD) and to monitor the efficiency of erythropoietin (EPO) treatment. The levels of sTfR reflect the receptor density on cells (tissue iron status) and the number of cells with receptors (erythropoietic activity). Currently assays for the measurements of sTfR are standardized using different reference materials, give different results, and have different reference ranges. The recent development of a lyophilized preparation of recombinant soluble transferrin receptor (rsTfR) as a World Health Organization (WHO) reference reagent should help in the standardization of sTfR immunoassays. This article reviews the general characteristics of (s)TfR, the assays for sTfR, biological confounders in the assays, and the clinical applications for measuring sTfR.     

转铁蛋白受体指数对儿童贮存铁减少的诊断价值

目的探讨转铁蛋白受体指数[血清转铁蛋白受体（sTfR）／Log血清铁蛋白（SF）]对儿童贫血早期贮存铁减少（IDS）诊断的有效性。方法检测568例武汉地区来我院的就诊儿童和96名健康儿童的锌原卟啉（ZPP）、血红蛋白（Hb）、血清铁蛋白（sF）、血清转铁蛋白受体（sTfR）水平。依评价标准，分为铁正常、IDS、红细胞生成缺铁（IDE）与缺铁性贫血（IDA）4组。统计IDS儿童数量，并计算其sTfR／LogSF。采用受试者工作特征（ROC）曲线分析sTfR、sTfR／LogSF诊断儿童IPS的效率。结果筛查出的102例IDS儿童与健康儿童相比，血清sTfR和sTfR／LogSF均显著增加（P〈0．05）。但对贫血早期儿童IDS的诊断而言。sTfR／LogSF的灵敏度、特异性、阳性预测值和阴性预测值均高于sTfR。经ROC曲线分析，sTfR诊断IDS的效率为0．79，而sTfR／LogSF诊断IDS的效率达0．93。结论sTfR／LogSF能有效反映儿童早期贮存铁的情况，可作为筛查儿童IDS的可靠指标。     

Soluble transferrin receptor and mutations in hemochromatosis and transferrin genes in a general Catalan population

BACKGROUND: The measurement of soluble transferrin receptor (sTfR) has been proposed as a valuable marker of erythropoietic activity and iron status. However, the possibility that mutations in HFE and/or transferrin genes have a direct effect on this parameter has not been sufficiently investigated. The present report addresses this point in the general population. METHODS: Serum sTfR, ferritin, iron and transferrin, as well as the H63D and the C282Y polymorphisms of the HFE gene and the TF C1/C2 polymorphism of the transferrin gene, were analysed in 348 subjects. RESULTS: We observed significant and independent associations of serum sTfR with sex (2.68+/-1.27 mg/L in men vs. 2.25+/-1.33 in women; P=0.002), H63D polymorphism (2.61+/-1.34 in wild type homozygotes vs. 2.28+/-1.25 in carriers of one or two mutated alleles; P=0.009), and serum iron concentration (r=-0.17; P=0.002). CONCLUSION: The H63D mutation of the HFE gene has a moderate but significant influence on sTfR concentration in the general population, the presence of one or two mutated alleles being associated with an average of 0.27 mg/L less sTfR than nonmutated homozygotes.     

C反应蛋白与血清铁参数联合检测在rHuEPO治疗肾性贫血中临床价值探讨

目的探讨C反应蛋白(CRP)与血清铁参数检测在重组人促红细胞生成素(rHuEPO)治疗肾性贫血(RA)中的临床应用价值。方法将75例RA患者按CRP水平分为Ⅰ组(CRP>8 mg/L)37例、Ⅱ组(CRP≤8 mg/L)38例。所有RA患者均应用rHuEPO治疗[80～120 U/(kg.周),分2次注射]。治疗前检测红系[红细胞(RBC)、血红蛋白(Hb)、红细胞压积(HCT)、网织红细胞计数百分比(RET%)]及铁代谢参数[血清转铁蛋白受体(sTfR)、血清铁(SI)、转铁蛋白饱和度(TS%)、血清铁蛋白(SF)]、CRP等指标,治疗后第24、8、周测定红系指标,第8周检测铁代谢参数,并进行统计学分析。结果 2组患者治疗前sTfR水平差异有统计学意义(P<0.05)。治疗后Ⅱ组红系指标及sTfR均升高,SF下降,与治疗前及Ⅰ组治疗后比较差异有统计学意义(P<0.05)。Ⅰ组CRP与Hb呈负相关(r=-0.55,P<0.01)、与SF呈正相关(r=0.65,P<0.01)。Ⅱ组sTfR与Hb呈正相关(r=0.71,P<0.01)、与SF呈负相关(r=-0.48,P<0.05)。结论血清铁参数与CRP等指标联合检测可指导rHuEPO的应用,对评价及预测其疗效有重要的临床意义。     

Evaluation of iron status of Finnish blood donors using serum transferrin receptor

The maximum allowable frequency of blood donations has been set so that donations should not cause anaemia or depletion of iron stores. However, it has not been determined precisely how often blood donations result in depletion of iron stores. In the present study we have evaluated iron status in blood donors using serum ferritin and transferrin receptor (TfR) concentrations. The elevation of serum TfR has been reported to be the most sensitive indicator of depletion of iron stores. On the basis of ferritin values, in men who donate frequently the amount of body iron is reduced to a level very close to that found in women donating blood for the first time. When an elevation of serum TfR above 4.0 mg L-1 was used as a stringent definition of complete iron depletion, it was estimated that 17% of frequently donating women had completely lost their iron stores, while the corresponding value for men was 8%. The fact that a considerable proportion of the female blood frequent donors have completely depleted their iron stores raises the question whether the iron status of female frequent blood donors should be routinely monitored using serum transferrin receptor measurements.     

可溶性转铁蛋白受体检测对非成年人缺铁性贫血的诊断价值

目的：探讨可溶性转铁蛋白受体（sTfR）对非成年人缺铁性贫血（IDA）的诊断价值及其与慢性病贫血（ACD）的鉴别诊断价值。方法 IDA 组26例,男12例,女14例,年龄1月至15．5岁;ACD 组33例,男17例,女16例,年龄2月至14．0岁;对照组30例,男15例,女15例,年龄1月至15．5岁。sTfR、铁蛋白（SF）检测方法为免疫比浊法,血清铁（SI）为亚铁嗪比色法。结果各组患儿的性别比例、年龄无显著性差异;ACD 组的 SI 均值介于 IDA 组和对照组之间;IDA 组的 SF 显著低于 ACD 组（P ＜0．001）和对照组（P ＜0．001）,而 sTfR 显著高于 ACD 组（P ＜0．001）和对照组（P ＜0．001）。sTfR 鉴别诊断 IDA 和 ACD 的截值为3．56 mg/L,其敏感性、特异性、阴性预测值、阳性预测值、准确性分别为95．12％、93．92％、94．11％、97．53％、95．50％。结论sTfR 对 IDA 具有较高的敏感性及特异性,有助于诊断 IDA 及鉴别诊断 ACD。     

可溶性转铁蛋白受体在缺铁性贫血诊断中的临床应用价值

目的探讨血清可溶性转铁蛋白受体(sTfR)在缺铁性贫血(IDA)诊断中的临床应用价值。方法选择正常对照组和IDA患者组各58例,同等条件下对2组sTfR、血清铁(Fe)、总铁结合力(TIBC)、转铁蛋白饱和度(TS)、转铁蛋白(Tf)、血清铁蛋白(SF)、血红蛋白(Hb)、平均红细胞容积(MCV)、平均红细胞血红蛋白量(MCH)、平均红细胞血红蛋白浓度(MCHC)、红细胞体积分布宽度(RDW)等指标进行定量检测,并分别行t检验和ROC曲线分析。结果 IDA组血清sTfR浓度为(46.40±9.43)nmol/L,正常对照组的sTfR浓度为(15.45±2.95)nmol/L,与对照组比较,IDA组血清sTfR明显升高,差异具有统计学意义(P<0.01)。用于IDA诊断时,sTfR的ROC曲线下面积达0.971(P<0.01)。结论血清sTfR浓度可较准确反映铁贮存状况,对IDA的诊断具有一定的临床实用价值。     

速率散射比浊法测定血清可溶性转铁蛋白受体及临床应用

目的评价速率散射比浊法测定血清可溶性转铁蛋白受体（sTfR）,并探讨sTfR在区分缺铁性贫血（IDA）与其他类型贫血中的作用。方法用速率散射比浊法测定IDA组、其他贫血组及正常对照组的血清sTfR,并按美国临床实验室标准化研究所（CLSI）评价方案系统评价其重复性、回收率、线性范围和溶血、脂血、胆红素对sTfR测定的干扰影响。结果速率散射比浊法测定血清sTfR在0.73～8.23mg/L内线性良好（线性回归方程为Y=1.031X-0.12,r=0.9978）,批内和批间变异系数（CV）均〈4%,回收率分别为94.2%和98.6%。干扰试验发现,胆红素〈325μmol/L、三酰甘油〈19.8mmol/L和血红蛋白〈5g/L对测定结果无明显干扰。IDA组血清sTfR的浓度为（2.89±1.31）mg/L,其他贫血组血清sTfR的浓度为（1.53±1.42）mg/L,正常对照组sTfR的浓度为（0.84±0.15）mg/L。与其他贫血组及对照组比较,IDA组血清sTfR明显升高,受试者工作特征（ROC）曲线下面积（AUC）达0.939（P〈0.01）。结论速率散射比浊法检测血清sTfR简单、快速、检测线性范围宽,能有效抵抗溶血、脂血、黄疸的干扰,在IDA的诊断及与其他贫血的鉴别诊断上有明显的实际应用价值,值得临床推广。     

Soluble transferrin receptor in hemochromatosis patients during phlebotomy therapy

BACKGROUND: The monitoring of phlebotomies in hemochromatosis patients depends on iron status measured by ferritin and transferrin saturation (TS). However, in the presence of inflammation or liver injury, soluble transferrin receptor (sTfR) determination was proposed to replace ferritin for diagnosing iron deficiency (ID). The present study evaluated performances of sTfR for the prediction of iron deficiency in a large number of hemochromatosis patients under phlebotomy therapy. METHODS: We studied 52 patients undergoing therapeutic phlebotomies and obtained 2 samples from 37 patients. Biological parameters were determined before each phlebotomy began. Performances of sTfR and TS in the diagnosis of iron deficiency were compared, according to ferritin levels under 12 microg/l. RESULTS: Ferritin and TS were correlated with removed iron (r=0.473, p<0.005 and r=0.345, p<0.05, respectively) and sTfR was correlated with the decrease in hemoglobin levels induced by phlebotomies (r=-0.678, p<0.0001). Areas under Receiver Operating Characteristics (ROC) curves for sTfR and TS were not statistically different for prediction of iron deficiency and sensitivity/specificity of sTfR at 1.64 mg/l were 67/86%. CONCLUSIONS: sTfR determination could be used to predict iron depletion induced by phlebotomies when ferritin is of limited interest, to avoid the appearance of anemia.