Progressive dysfunction of monocytes associated with iron overload and age in patients with thalassemia major

Ballart, IJ; Estévez, María; Sen, Luisa; Diez, RA; Giuntoli, J; Miani, S; Peñalver, Javier

doi:10.1182/blood.v67.1.105.105

Cited by 43 publications

(10 citation statements)

References 20 publications

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“…The reduced killing activity of PMN was observed at 60 min of incubation. 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).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2007

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Flow cytometric assays for quantifying polymorphonuclear leucocyte (PMN) function involve peripheral blood fractionation methods. However, most are of limited use for conditions like pediatrics and thalassemia, as they may require large blood volumes or complicated by red blood cell contamination. In whole blood assay, 500-ll aliquots of normal or thalassemic whole blood were incubated with bis-carboxyethyl-carboxyfluorescein pentaacetoxymethylester (BCECF-AM)-labeled Candida albicans cells and phycoerythrin-conjugated anti-CD13 monoclonal antibody for PMNs. Phagocytosis was quantitated by gating on CD13 label PMNs and determining the frequency of phagocytosed yeast using flow cytometry. The killing activity was quantitated by estimating the number of viable fluorescence retaining yeast cells liberated following lysis of PMNs. In normal control or thalassemia samples, nonphagocytosed yeast and PMNs with or without phagocytosed yeast were readily distinguished by two-color dot plot, permitting phagocytosis estimates. Viable and nonviable yeast killed by whole blood PMNs were distinguished by side scatter and fluorescence, permitting killing estimates. The patterns seen using whole blood was similar to that seen with fractionated PMNs. Data from thalassemia patients showed similar opsonophagocytosis but slightly decreased intracellular killing of yeast cells when compared with normal subjects. This assay provides an alternative method to assess PMN function in small blood samples, which could be especially useful in conditions like thalassemia and pediatric patients. ' International Society for Analytical CytologyKey terms bis-carboxyethyl-carboxyfluorescein pentaacetoxymethylester; Candida albicans; flow cytometry; phagocytes; phagocytosis; polymorphonuclear leucocytes; thalassemia NEUTROPHILS, also called polymorphonuclear leucocytes (PMNs), are first-line defenses against invading microorganisms. Various flow cytometric or whole blood fractionation methods exist to assess PMN function (1-8), but most require relatively large numbers of PMNs, making them impractical for pediatric blood samples. In addition, the assays perform poorly on samples from patients with hematological conditions such as thalassemia. Moreover, fractionating PMNs from blood is time consuming and the procedure used can itself trigger PMN activation.Whole blood assays are simple, convenient, and generally require small volumes. Here, we describe a rapid, simple, and reliable flow cytometric technique for measuring opsonophagocytosis and killing of Candida albicans (C. albicans) by PMNs using a whole blood assay. In efforts to validate the technique, PMNs derived from whole blood samples and, for purposes of comparison, dextran fractionation preparations contaminated with non-PMNs were assayed for PMN function using our whole blood assay utilizing blood samples from patients with thalassemia, an inherited autosomal recessive hemolytic anemia associated with impaired globin chain synthesis. PMN fractionation by the dextran sedimentat...

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Section: Discussionmentioning

confidence: 99%

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

et al. 2007

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“…[36][37][38][39][40][41][42] Immune dysfunction and increased susceptibility to infection also has been demonstrated in patients and animals with secondary forms of iron overload. 29,[43][44][45][46][47][48][49] Enhanced iron-dependent microbial growth in combination with defects in cell-mediated immunity and impaired phagocytosis may have contributed to the mortality from infection in our patient population.…”

Section: Discussionmentioning

confidence: 99%

Iron overload in cirrhosis— HFE genotypes and outcome after liver transplantation

et al. 2000

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Previously, we found appreciable hepatic iron deposition in one third of our patients undergoing liver transplantation (LTx) with approximately 10% of cases having quantifiable iron in the range of that seen in hereditary hemochromatosis (HHC). The aim of this study was to compare clinical outcome in liver transplant patients with and without iron overload. We also sought to determine the prevalence of HFE mutations in liver transplant patients with iron overload. Of 456 consecutive liver transplants, 41 explants had an hepatic iron index (HII) greater than 1.9, and these cases were compared to 41 matched liver transplant recipients without increased hepatic iron. Posttransplantation complications, along with patient and graft survival were monitored. HFE gene testing was performed using DNA-based techniques. Kaplan-Meier 5-year patient survival after LTx was significantly lower in cases with hepatic iron overload compared to matched controls without iron excess (48% vs.

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“…Neutrophil function is impaired (32)(33)(34). Peripheral blood monocytes show impaired lytic activity (35) and natural killer cells show impaired activity against target cells (36).…”

Section: Iron Statusmentioning

confidence: 99%

Iron and Infection: The Clinical Evidence

1989

Acta Paediatrica

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Oppenheimer, S. J. (Department of Paediatrics, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia). Iron and infection: The clinical evidence. Iron deficiency is prevalent in childhood in the developed and developing countries. Programs of presumptive therapy, mass supplementation and food fortification have been introduced in many countries. The unresolved debate over the interaction of iron and infection in the clinical setting prompts re‐evaluation of these practices. Situations of iron overload are associated with increased susceptibility to certain infections, although the exact mechanisms may vary with the main pathology. Iron treatment has been associated with acute exacerbations of infection, in particular malaria. In most instances parenteral iron was used. In the neonate parenteral iron is associated with serious E. coli sepsis. In one country, with endemic malaria, parenteral iron was associated with increased rates of malaria and increased morbidity due to respiratory disease in infants. In contrast in non‐malarious countries studies of oral iron supplementation have if anything shown a reduction in infectious morbidity. Methodological problems in the latter reports indicate the need for further controlled prospective studies with accurate morbidity recording if informed recommendations are to be made.

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Progressive dysfunction of monocytes associated with iron overload and age in patients with thalassemia major

Cited by 43 publications

References 20 publications

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

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

Iron overload in cirrhosis— HFE genotypes and outcome after liver transplantation

Iron and Infection: The Clinical Evidence

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