Neutrophil dysfunctions in thalassaemia major: The role of cell iron overload

Abstract

The susceptibility to infections was recorded in 13 patients with I3 thalassaemia major (T.P.). The following parameters were also investigated in their polymorphonuclear neutrophils (PMN): nitro blue tetrazolium (NBT) reduction, heated yeast and Escherichia coli phagocytosis, Escherichia coli killing and myeloperoxydase activity. These results were compared to those obtained in healthy controls (H.C.). The Perk's reaction was performed on PMN and graded according to a scoring system with the aim of quantifying the iron intoxication of PMN. Phagocytosis and Perk's reaction of PMN from H.C. were also studied after 20 h of incubation with thalassaemic serum. 6 T.P. out of 13 developed septicaemia during their lifetime and in all 9 septicaemic episodes were noted. Phagocytosis was greatly impaired, disclosing both cellular and serum abnormalities. The mean percentage of Perk's positive PMN was 13% in T.P., contrasting with the constant negative reaction in H.C. The incubation of PMN from H.C. with serum from T.P. induced the simultaneous appearance of a phagocytosis defect and of a positive Perl's reaction. It was concluded that in I3 thalassaemia major the phagocytosis of PMN was altered due to a combination of serum and cellular abnormalities and that both may be related to the iron overload.

Flow cytometric quantitation of opsonophagocytosis and intracellular killing of Candida albicans using a whole blood microassay

“…A number of investigators have shown that ingestion of C. albicans by PMNs of thalassemia patients was normal (17–19). However, these data were different from others who utilized Escherichia coli , baker's yeast (16, 20, 21), Salmonella typhi , and Staphylococcus aureus (22). The differences could be due to the use of different kinds of organisms and different methodologies used in these experiments.…”

“…Our whole blood study used 40–50% of autologous plasma which not only mimics the plasma concentration in vivo, but also contains enough opsonins and other physiological concentration of factors such as extracellular calcium for such initiation process. Study in thalassemia patients showed that 10–20% of autologous serum or plasma was enough to obtain maximum phagocytosis and intracellular killing of Escherichia coli and yeast cells (16). This assay should provide an improved physiological milieu to include the presence of soluble factors necessary for opsonization of microorganisms and regulation of PMN function.…”

mmunologic Abnormalities in β-Thalassemia

“…It was established that iron and its protein compounds have immunoregulatory characters, and therefore, an excess of iron may adversely affect the immune balance [37]. Numerous studies have shown the negative effect of excess iron on immunological functions, which include suppression of monocyte-macrophage system, changes in subpopulations of T-lymphocytes increasing CD8 and suppression of CD4, increased secretion of immunoglobulins and inhibiting the function of the complement system [16,[37][38][39].…”

“…In addition, phagocytosis of microorganisms, dyserythroportic precursors and aging or damaged red blood cells (inside and/or outside the vessel) produces oxidative stress [40]. The fact that the excess of iron has a negative effect on the function of PMN and inhibites phagocytosis indicated above [13,14,[16][17][18].…”

“…Skoutelis et al [15] conducted the study PMN in 50 patients with homozygous thalassemia and identified disorders of phagocytic and bactericidal functions of these cells and related them to iron overload. Cantinieaux et al [16,17] conducted a study to identify relationship between phagocytic function disorders in patients with thalassemia major and iron overload. The authors showed that in 13% of PMN of patients with thalassemia Perls reaction were positive, whereas in the control group were no positive result for iron cells.…”