Immunological Reactivity of Serum Ferritin in Patients with Malignancy

Abstract

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: an immunoradiometric assay based on polyclonal antibodies against human liver (basic, L-subunit rich) ferritin, a radioimmunoassay based on polyclonad antibodies against HeLa cell (acidic, H-subunit rich) ferritin, and 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 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 or monitoring of malignant disease. This seems to be due to the presence in human serum of biding 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.

The Interaction of the Antitumor ComplexesNa[trans‐RuCl4(DMSO)(Im)] and Na[trans‐RuCl4(DMSO)(Ind)] WithApotransferrin: a Spectroscopic Study

“…Traces a, b, c in Figure B were recorded at 3, 10 and 30 minutes after mixing. Trace d was recorded the day after.Conditions: [11] To better elucidate the formation of specific adducts between complexes and II and apoTf we analyzed the final hydrolysis products obtained both in the absence and in the presence of apoTf, by CD spectroscopy. CD spectroscopy is a valuable tool to demonstrate the specific binding of small metal complexes, with transitions in the visible region, to chiral biomolecules19.…”

Biology of ferritin in mammals: an update on iron storage, oxidative damage and neurodegeneration

“…Ferritins are found also in other cellular compartments (lysosomes and nucleus), in extracellular fluids and in the blood. Serum ferritin is predominantly made by L subunits (Cazzola et al 1985;Santambrogio et al 1987) and is a significant clinical parameter for the diagnosis and monitoring of iron overload or deficiency. Different reviews dealt with this topic (Wang et al 2010;Ferraro et al 2012) that will be not further considered in this manuscript.…”

Fluctuations of Intracellular Iron Modulate Elastin Production

“…To test this we utilized a highly specific membrane-permeable ferric iron chelator, DFO, which have been shown to deplete intracellular pools of free iron (53)(54)(55). Results of immunocytochemistry (Fig.…”