IMMUNOLOGICAL REACTIVITY OF SERUM FERRITIN IN PATIENTS WITH MALIGNANCY

IMMUNOLOGICAL REACTIVITY OF SERUM FERRITIN IN PATIENTS WITH MALIGNANCY
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DOI:
10.1177/030089168507100606
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发表时间:
1985-01-01
期刊:
影响因子:
1.9
通讯作者:
ASCARI, E
ASCARI, E
中科院分区:
医学4区
文献类型:
--
作者:
CAZZOLA, M;AROSIO, P;ASCARI, E

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血清铁蛋白已被认为是诊断某些恶性肿瘤和跟踪恶性过程的活动或传播的肿瘤标志物。由于肿瘤组织通常比正常组织含有更多的酸性异铁蛋白,因此也有人认为,血清中这种异铁蛋白的特异性测定可能在恶性肿瘤的诊断中具有特殊的价值。在这项工作中,我们通过同时使用三种不同的免疫分析法,评估了正常人和急性非淋巴细胞白血病、霍奇金病、乳腺癌和肺癌患者血清中的铁蛋白浓度:(a)基于针对人肝脏(碱性,富含l亚基)铁蛋白的多克隆抗体的免疫放射测定,(b)基于针对HeLa细胞(酸性,富含h亚基)铁蛋白的多克隆抗体的放射免疫测定,以及(c)基于针对人心脏(酸性,富含h亚基)铁蛋白的单克隆抗体2A4的免疫放射测定。大多数被研究的患者在没有铁储存增加的情况下肝型铁蛋白升高。血清铁蛋白与刀豆蛋白A的结合在区分肿瘤特异性碱性异铁蛋白方面没有被证明是有用的。在检测酸性异铁蛋白方面,HeLa铁蛋白试验的特异性低于心脏铁蛋白试验,并且在检测与恶性疾病相关的血清铁蛋白水平升高方面,与肝脏铁蛋白试验相比,没有任何优势。在五分之一的正常血清和64%的恶性肿瘤患者血清中发现心脏型铁蛋白。与恶性肿瘤患者的基础血清相比,该值非常低。与碱性铁蛋白相比,碱性铁蛋白的值非常低,在恶性肿瘤患者中,碱性铁蛋白占血清总铁蛋白的比例在0.1%至17%之间(几何平均值1.3%)。这些结果表明,目前基于HeLa细胞抗体或心脏铁蛋白抗体的血清铁蛋白免疫测定在恶性疾病诊断监测中的应用很少。这似乎是由于人血清中存在一种结合因子,这种结合因子负责从循环中快速清除酸性异铁蛋白。然而,碱性铁蛋白的血清浓度可用于某些恶性肿瘤的诊断和治疗,并且细胞异铁蛋白的研究可能在肿瘤疾病的生物学监测中具有重要意义。还应注意的是,恶性肿瘤患者血清铁蛋白水平升高可能对宿主免疫反应产生不利影响,并可能对造血产生抑制作用。
Serum ferritin has been suggested as a tumor marker in the diagnosis of certain malignancies and for following the activity or dissemination of the malignant process. Since neoplastic tissues generally contain more acidic isoferritins than their normal tissue counterparts, it has also been suggested that the specific assay of such isoferritins in serum may be of particular value in the diagnosis of malignancy. In this work, we have evaluated ferritin concentration in the serum of normal subjects and patients with acute nonlymphocytic leukemia, Hodgkin''s disease, breast cancer and lung cancer by simultaneously using three different immunoassays: (a) an immunoradiometric assay based on polyclonal antibodies against human liver (basic, L-subunit rich) ferritin, (b) a radioimmunoassay based on polyclonal antibodies against HeLa cell (acidic, H-subunit rich) ferritin, and (c) an immunoradiometric assay based on the monoclonal antibody 2A4 raised against human heart (acidic, H-subunit rich) ferritin. Most of the patients studied had increased values for liver-type ferritin in the absence of increased iron stores. Binding of serum ferritin to concanavalin A did not prove to be useful in distinguishing a tumor-specific basic isoferritin. The HeLa ferritin assay was found to be less specific than the heart ferritin assay in the detection of acidic isoferritins, and did not provide any advantage over the liver assay in detecting the increased levels of serum ferritin associated with malignant disease. Heart-type ferritin was found in one-fifth of normal sera and 64% of sera from patients with malignancy. Values were very low compared with those for basic sera from patients with malignancy. Values were very low compared with those for basic ferritin, ranging from less than 0.1 to 17% of total serum ferritin (geometric mean value 1.3%) in patients with malignancy. These findings indicate that at present there is little application for serum ferritin immunoassays based on antibodies to HeLa cell or heart ferritin in the diagnosis of monitoring of malignant disease. This seems to be due to the presence in human serum of binding factors which are responsible for the rapid clearance of acidic isoferritins from the circulation. The serum concentration of basic ferritin, however, can be useful in the diagnosis and management of some malignancies, and it is possible that studies on cell isoferritins can be important in biologic monitoring of neoplastic disorders. It should also be noted that the increased levels of serum ferritin found in patients with malignancy can exert adverse effects on the host immune response and perhaps an inhibitory effect on hematopoiesis.