Division of Immunology, University Children's Hospital and Children's Research Centre, Zurich, Switzerland.
Division of Infectious Diseases and Immunology, Dr. von Haunersches Kinderspital, University Childrens Hospital, Ludwig-Maximilians-University, Munich, Germany.
J Allergy Clin Immunol. 2017 Jan;139(1):212-219.e3. doi: 10.1016/j.jaci.2016.04.041. Epub 2016 Jul 22.
Glucose-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.
We sought to study the molecular pathophysiology leading to susceptibility to infection in 3 siblings with severe G6PD deficiency.
Blood 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.
In 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.
Because 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.
葡萄糖-6-磷酸脱氢酶（G6PD）缺乏症是人类红细胞最常见的酶缺陷疾病，可导致溶血性贫血，与 NADPH 生成受损和红细胞内氧化还原平衡失调有关。由于 G6PD 由多种血液和非血液细胞表达，因此推测 G6PD 缺乏症患者可能具有更广泛的临床表型。我们描述了 3 名患有严重 G6PD 缺乏症和易发生细菌感染的兄弟。
我们旨在研究导致 3 名严重 G6PD 缺乏症患者易发生感染的分子病理生理学机制。
分析 3 名严重 G6PD 缺乏症患者的血液样本，以检测 G6PD 酶活性、细胞内氧化型烟酰胺腺嘌呤二核苷酸磷酸（NADP+）/NADPH 水平、吞噬细胞产生的活性氧物质、中性粒细胞胞外陷阱（NET）形成和中性粒细胞弹性蛋白酶转位。
在这 3 位兄弟中，发现粒细胞 NADPH 氧化酶功能严重降低，导致 NET 形成受损。到目前为止，只有 NADPH 氧化酶缺陷性慢性肉芽肿病患者才观察到 NET 形成缺陷，这些患者需要抗生素和抗真菌药物预防，以预防危及生命的细菌和真菌感染。
由于严重 G6PD 缺乏症在细胞和临床表型方面可能是慢性肉芽肿病的表型，因此在这些患者中，似乎需要仔细评估中性粒细胞功能，以决定是否需要采取适当的抗感染预防措施。确定 G6PD 酶活性水平后，应分析活性氧物质的产生和 NET 形成，以决定是否需要抗生素和抗真菌药物预防。
