concanavalin-a and Thalassemia

To evaluate natural killer cytotoxicity (NKC) and its regulation by interferon (IFN) in thalassemia major (TM), we studied 19 patients, 10 carriers (parents of 10 different patients) and 35 normal subjects (children and adults) as controls. We have found a diminished NKC, as well as a decrease in the percentages of cells bearing IgGFc receptors in TM patients, whereas they were normal in TM carriers. Although alpha-IFN enhanced NKC in TM patients and carriers, Con A (an IFN inducer) had no enhancing effect on NKC from either patients or carriers. These agents did not modify the expression of IgGFc receptors in cells from TM patients, carriers or normal controls. Our results indicate that TM patients have a defect in NK cell maturation or activation, which is reversed by alpha-IFN. The failure of TM patients and carriers to respond to Con A suggests a defect in NKC regulation which might be related to a genetic origin.

Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Concanavalin A; Cytotoxicity Tests, Immunologic; Cytotoxicity, Immunologic; Female; Genetic Carrier Screening; Humans; Infant; Interferon Type I; Killer Cells, Natural; Male; Middle Aged; Monocytes; Receptors, Fc; Thalassemia

Liver and spleen iron concentrations, serum ferritin level and binding of S-ferritin to concanavalin A (Con A) were measured in 12 patients with thalassaemia major or intermedia at the time of splenectomy. All these subjects had increased liver iron concentration, most of them had hepatic fibrosis but none of them had histological evidence of chronic hepatitis. No patient had ascorbic acid deficiency. Serum ferritin concentration was increased in all cases, ranging from 266 to 5504 micrograms/l. In all but 2 subjects most of the protein did not bind to Con A, thus behaving as tissue ferritin. There were highly significant correlations between serum ferritin concentration, amount of blood transfused and liver iron concentration. On the average, iron concentration in the liver was about 3 times that in the spleen. The findings obtained suggest that in patients with thalassaemia major or intermedia most of the iron is deposited in parenchymal tissues and most of the S-ferritin derives by leakage from the cytosol of iron-loaded parenchymal cells. S-ferritin is a valid index of liver iron overload in thalassaemic patients without complications such as viral hepatitis and/or ascorbic acid deficiency.

Topics: Blood Transfusion; Concanavalin A; Ferritins; Humans; Iron; Liver; Spleen; Thalassemia

Total serum ferritin and the proportion of serum ferritin binding to concanavalin A (glycosylated ferritin) was measured in 18 healthy volunteers and in 84 patients, eight with primary haemochromatosis, 43 with beta-thalassaemia major and secondary iron overload and 33 with chronic liver diseases without iron overload. The total serum ferritin was either equally or even more closely related than either the non-binding or the concanavalin A binding ferritin, to the liver iron concentration in all patients with iron overload, and with the units of blood transfused in non-chelated thalassaemic patients. The total serum ferritin showed a significant correlation with serum aminotransferase for the group of 84 patients. In the thalassaemic patients the ferritin binding to concanavalin A also correlated with aminotransferase. However, in the other groups it was the ferritin not binding to concanavalin A which showed a significant correlation with aminotransferase activity. These results suggest that measuring the fraction of serum ferritin which binds to concanavalin A does not offer any advantage over estimation of the total serum ferritin concentration in the assessment of iron stores in patients wit iron overload and liver damage.

Topics: Binding Sites; Chronic Disease; Concanavalin A; Ferritins; Hemochromatosis; Humans; Iron; Liver; Liver Diseases; Thalassemia; Transaminases

Ten thalassemia intermedia patients were tested for their mitogenic responses to phytohemagglutinin P (PHA), concanavalin A (Con A) and pokeweed mitogen (PWM). Impaired responses to PHA and Con A were observed in patients with serum-iron levels higher than 200 microgram/dl. Responses within or slightly higher than those in the normal range were observed in patients with serum-iron lower than 200 microgram/dl. By contrast, no significant changes occurred in the majority of the responses to PWM.

Topics: Adolescent; Adult; Child; Concanavalin A; Dose-Response Relationship, Immunologic; Ferric Compounds; Humans; Iron; Mitogens; Phytohemagglutinins; Pokeweed Mitogens; T-Lymphocytes; Thalassemia

Serum ferritin concentrations have been measured in 124 patients with homozygous beta thalassaemia who were between 2 and 21 years old, had received 11--504 units of blood but had not undergone splenectomy. There were highly significant correlations between serum ferritin concentration and both the amount of blood transfused and alanine amino-transferase (ALT) activity. However, multivariate analysis showed that units of blood and ALT activity together only accounted for about 30% of the variation in serum ferritin concentration. Little of the remaining variation could be explained by other variables related to iron metabolism or liver damage. The concentration of concanavalin A binding ferritin increased rapidly with the number of units of blood up to 100 units but thereafter showed no further increase with number of transfusions. The concentration of non-binding ferritin was more closely related to transfusion load. These results suggest that the secretion of glycosylated ferritin from reticuloendothelial cells reaches a maximum with increasing iron accumulation, perhaps reflecting a maximum rate of synthesis. Ferritinaemia in patients with transfusional iron overload therefore seems to be the result of the combined effects of increased ferritin synthesis and the release of intracellular ferritin from damaged cells. A simple relationship between serum ferritin and iron stores cannot be assumed when ferritin concentrations exceed 4000 microgram/l or in patients who have received more than 100 units of transfused blood.

Topics: Adolescent; Adult; Alanine Transaminase; Child; Child, Preschool; Concanavalin A; Ferritins; Homozygote; Humans; Iron; Thalassemia; Transfusion Reaction