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We evaluated the phagolysosomal fusion of peripheral blood monocytes from 15 patients with thalassemia major and 10 thalassemia major carriers using a cytomorphological method with acridine orange as fusion marker. The monocyte phagolysosomal fusion of thalassemic patients was decreased (49.6 +/- 8.6%, mean +/- SD) and differed significantly (p < 0.05) from those of carriers and normal controls (65.7 +/- 11.4% and 74.6 +/- 5.7%, respectively). In vitro deferoxamine partially improved monocyte phagolysosomal fusion of patients with thalassemia major, and did not affect monocyte function in carriers and healthy subjects. Furthermore, in vitro addition of ferrous sulfate decreased normal phagolysosomal fusion. We conclude that the monocyte phagolysosomal fusion dysfunction of thalassemic patients could be related to iron overload.

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PURPOSE: To evaluate the chemotactic capability of neutrophils in thalassaemic patients under poly-transfusion regimens and in thalassaemia carriers. PATIENTS AND METHODS: Twenty-one patients in multi-transfusion regimen diagnosed in the Ricardo Gutiérrez Children Hospital were studied. Of them, 17 had thalassaemia major, 3 S/beta thalassaemia and one sickle-cell anaemia. Twenty-one normal subjects comprised a control group. Chemotaxis was evaluated by two methods, namely, migration under agarose layer and in microchemotaxis chamber under stimulation with N-formyl-methionyl-n-phenylalanine at optimal concentrations of 10(-5) M and 10(-6) M, respectively. RESULTS: In thalassaemia major patients, directed mobility of neutrophil assessed by both methods was significantly decreased with regard to the normal controls, whereas random mobility was preserved. The four patients under poly-transfusion who had not thalassaemia major showed the same neutrophil defect. On the contrary, chemotaxis and random mobility of the neutrophils from thalassaemia carriers (thalassaemia minor) were similar to those of the normal controls. CONCLUSIONS: These results suggest that the defect found in the patients might be caused by transfusion overload.

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We studied the ability of B-lymphocytes to differentiate to immunoglobulin-producing cells in 14 patients with thalassemia major, 11 parents of the patients, and 86 normal subjects. In comparison with the parents of the patients and with the normal individuals, the patients were found to have 1) an increased number of cells spontaneously secreting immunoglobulin; 2) a decreased number of plaque-forming cells (PFC) when induced with pokeweed mitogen (PWM) and a deficient helper T-cell function for the induction of B-cell differentiation; 3) an increase in the number of PFC after the addition of alpha interferon (100 IU/ml) to the cell cultures with PWM. Previous incubation of non-T-cells with alpha interferon for 1 hr and subsequent coculture with T-cells from the same patients or from normal subjects in the presence of PWM increased the number of PFC. On the contrary, previous incubation of T-cells with alpha interferon followed by coculture with normal non-T-cells or cells from the same patient did not modify the number of PFC. These results suggest that patients with thalassemia major possess hyperreactive spontaneous B-cell responses and that these B-cells are unable to differentiate to immunoglobulin-secreting cells in the presence of PWM. This would be due to a T-helper-cell deficiency with an inability to produce lymphokines (interferon being one of them), while the B-cell function seems to remain intrinsically intact.

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We evaluated phagocytic and lytic activities of peripheral blood monocytes (PBMo) from patients with thalassemia major (ThP) using C pseudotropicalis as the target. PBMo from ThP showed decreased lytic activity (P less than .001), whereas the phagocytic activity did not differ from that of the controls. Significant inverse correlations were found between lytic activity of PBMo and age of patients (r2 = .47; P less than .01) and also between lytic activity and serum ferritin levels (r2 = .65; P less than .001). No association was found between lytic activity and other variables (blood transfusion regimens, therapy with desferrioxamine, liver damage, and the presence of sHBAg). Splenectomy showed no positive effect on PBMo functions from ThP. Our results suggest that PBMo from ThP have an intracellular defect in their microbicidal mechanisms associated with iron overload. This cell dysfunction could be responsible, at least in part, for the increased susceptibility to infections reported in ThP.

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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.

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