Mark Worwood

Serum ferritin concentration and iron stores in normal subjects

The relationship between serum ferritin concentration and the amount of storage iron has been studied in normal subjects. A high degree of correlation was demonstrated between serum ferritin concentration and storage iron measured by quantitative phlebotomy. The possible advantages of assessing iron stores by using the serum ferritin concentration are discussed.

Ferritin in the Serum of Normal Subjects and Patients with Iron Deficiency and Iron Overload

The concentration of ferritin in serum gives a quantitative measure of the amount of storage iron in normal subjects and those with iron deficiency or overload. The mean level in normal men is 69 ng/ml, compared with 35 ng/ml in normal women. A concentration below 10 ng/ml is associated with a low transferrin saturation and iron-deficient erythropoiesis.

Ferritin in serum.

FERRITIN is the major iron storage protein in the body. Although it is found in all tissues there is little quantitative information about its distribution. Measurements of non-heme iron concentrat...

An immunoradiometric assay for the acidic ferritin of human heart: application to human tissues, cells and serum.

Human tissues contain ferritin molecules with a range of isoelectric points but immunoassays for detecting serum ferritin have generally employed antibodies to the more basic liver or spleen proteins. To study the distribution of more acidic ferritins in tissues and serum acidic ferritin has been isolated from normal human heart and a two-site immunoradiometric assay for this protein developed. This assay gives little cross-reaction with spleen ferritin. Tissue ferritins have been fractionated by anion exchange chromatography and assayed with both spleen and heart antibodies. The spleen ferritin assay detects the more basic ferritin and the heart ferritin assay the more acidic ferritin. Acidic ferritins were found in heart, kidney, reticulocytes and HeLa cells. In sera from normal subjects and patients with iron overload, myocardial infarction, leukaemia and carcinoma only low concentrations of heart ferritin were found, although in the pathological sera spleen ferritin concentrations were generally raised. Circulating ferritin contains only a small proportion of molecules with the immunological characteristics of acidic heart ferritin.

Ferritin in Normal Erythrocytes, Lymphocytes, Polymorphs, and Monocytes

Summary. A method has been devised for the separation of red cells, polymorphs, lymphocytes, and monocytes from the peripheral blood. The fractions give a large yield of cells with a high degree of purity, and cells appear to be undamaged.

Serum ferritin in patients with cancer: determination with antibodies to hela cell and spleen ferritin

Some malignant tissues and cell lines contain acidic isoferritins and it has been suggested that the assay of such isoferritins in serum may be of value in the diagnosis of malignancy. This paper describes a radioimmunoassay for acidic ferrtin purified from HeLa cells. Examiniation of purified heart, kidney, liver and spleen ferritin showed that the assay was highly specific for acidic isoferritins. Ferritin concentrations have been measured with antibodies to HeLa cell and spleen ferritin in extracts of normal and tumour tissue. Although the tumours contained more HeLa type ferritin than the corresponding normal tissue the HeLa/spleen type ferritin ratio was low. HeLa-type ferritin concentrations have been compared with values obtained with anti-spleen ferritin in over 1000 sera from normal subjects and patients with cancer and leukaemia. HeLa-type ferritin as not detected ( less than 2 micrograms/l) in most normal sera. Concentrations of up to 53 micrograms/l were found in sera from patients with malignant disease but the HeLa/spleen type ferritin ratio was always very low. There appears to be little application for antibodies to HeLa cell or heart ferritin in the diagnosis or monitoring of cancer.

Ferritin in Blood Cells from Normal Subjects and Patients with Leukaemia

Summary. Normal human leucocytes contain about 7 fg ferritin protein per cell. In 16 patients with acute myeloblastic leukaemia the mean concentration was 46 fg per cell, in acute myelomonocytic leukaemia 175 fg per cell, and in chronic granulocytic leukaemia 16 fg per cell.

Accumulation and release of isoferritins during incubation in vitro of human peripheral blood mononuclear cells

Summary Ferritin concentration has been measured in peripheral blood mononuclear cells and in the incubation medium following in vitro culture. Antibodies to both heart and spleen ferritin were used. Mononuclear cells cultured in medium containing about 12 μmol Fe/1 accumulate ferritin rapidly with an increase in the heart:spleen ferritin ratio from 3:1 to about 10:1. Higher concentrations of iron (100 μmol/1) produce an even greater effect. The accumulation of ferritin is prevented by the addition of desferrioxamine (2 mmol/1) to the incubation medium. Accumulation of ferritin appears to take place largely in monocytes. Phagocytosis of red blood cells also causes rapid accumulation of ferritin but without any change in the heart: spleen ratio. Small amounts of both spleen and heart type ferritin are released during incubation in an iron containing medium and following phagocytosis of red blood cells. Some concanavalin A binding ferritin is also released suggesting that phagocytic cells may be a source of the concanavalin A binding ferritin found in normal plasma.

Human major histocompatibility complex contains several leukemia susceptibility genes.

In mice, homozygosity for the Mhc haplotype H-2k is associated with increased susceptibility to spontaneous and virus-induced leukemia, lymphoma and other neoplasms in the predisposed host. The influence of the Mhc on malignant development in these models is to shorten the latency after virus inoculation. Here, we present evidence that a similar phenomenon results in early-onset of human leukemia. A molecular analysis of the MHC in 112 CML patients showed that those who developed the disease when aged less than 35 years (early-onset group) had higher homozygosity rates for the DOA1, HSP70 and C4 alleles of the DR53 group of ancestral haplotypes, for a subtype of HLA-A3, and a higher allele frequency of BfFb compared to the late-onset group. The oldest patient (n = 13) homozygous for DR53 was 52-years-old (p = 0.004), and all HLA-A3 homozygous patients (n = 4) were in the early-onset group (p = 0.01). The relative risk for early-onset CML yielded by HLA-A3 homozygosity was 17.6. The well-known serological HLA-Cw4 association was not confirmed at the DNA level and thought to be due to linkage disequilibrium with BfFb. The factor B association was sex-limited. The DR52 group haplotypes appeared to be protective. The HLA-identical sibling frequency was increased only in the early-onset group (p < 0.01). Our findings agree with the concept of an MHC influence on the development of malignancies. The similarity in the location of the susceptibility loci and the serological cross-reaction between H-2Ek and DR53 raise the possibility that the mouse and human MHC share the same leukemia susceptibility genes.

The iron content of intestinal epithelial cells and its subcellular distribution: studies on normal, iron-overloaded and iron-deficient rats.

Summary. Small intestinal epithelial cells from normal, iron‐loaded and iron‐deficient rats were homogenized and fractionated by differential centrifugation. The iron content of the fractions was measured together with the activities of two iron containing enzymes, succinic dehydrogenase and cytochrome oxidase. A comparison of the values obtained from the iron‐overloaded rats with controls showed no significant increase in either the iron content or the enzyme activities. However, the iron‐deficient rats showed a marked decrease in both. In all three cases the concentration of iron was particularly high in the mitochondrial fraction. In irondeficient epithelial cells mitochondrial enzyme activity appeared in the soluble fraction suggesting mitochondrial damage.