Severe glucose-6-phosphate dehydrogenase deficiency leads to susceptibility to infection and absent NETosis

Publication date: Available online 22 July 2016
Source:Journal of Allergy and Clinical Immunology
Author(s): Ulrich Siler, Susana Romao, Emilio Tejera, Oleksandr Pastukhov, Elena Kuzmenko, Rocio G. Valencia, Virginia Meda Spaccamela, Bernd H. Belohradsky, Oliver Speer, Markus Schmugge, Elisabeth Kohne, Manfred Hoenig, Joachim Freihorst, Ansgar S. Schulz, Janine Reichenbach
BackgroundGlucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymatic disorder of red blood cells in human subjects, causing hemolytic anemia linked to impaired nicotinamide adenine dinucleotide phosphate (NADPH) production and imbalanced redox homeostasis in erythrocytes. Because G6PD is expressed by a variety of hematologic and nonhematologic cells, a broader clinical phenotype could be postulated in G6PD-deficient patients. We describe 3 brothers with severe G6PD deficiency and susceptibility to bacterial infection.ObjectiveWe sought to study the molecular pathophysiology leading to susceptibility to infection in 3 siblings with severe G6PD deficiency.MethodsBlood samples of 3 patients with severe G6PD deficiency were analyzed for G6PD enzyme activity, cellular oxidized nicotinamide adenine dinucleotide phosphate/NADPH levels, phagocytic reactive oxygen species production, neutrophil extracellular trap (NET) formation, and neutrophil elastase translocation.ResultsIn these 3 brothers strongly reduced NADPH oxidase function was found in granulocytes, leading to impaired NET formation. Defective NET formation has thus far been only observed in patients with the NADPH oxidase deficiency chronic granulomatous disease, who require antibiotic and antimycotic prophylaxis to prevent life-threatening bacterial and fungal infections.ConclusionBecause severe G6PD deficiency can be a phenocopy of chronic granulomatous disease with regard to the cellular and clinical phenotype, careful evaluation of neutrophil function seems mandatory in these patients to decide on appropriate anti-infective preventive measures. Determining the level of G6PD enzyme activity should be followed by analysis of reactive oxygen species production and NET formation to decide on required antibiotic and antimycotic prophylaxis.



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