title: Infections associated with chronic granulomatous disease: linking genetics to phenotypic expression.
abstract: Chronic granulomatous disease (CGD) is an inherited primary immunodeficiency characterized by the absence or malfunction of the NADPH oxidase in phagocytic cells. As a result, there is an impaired ability to generate superoxide anions and the subsequent reactive oxygen intermediates. Consequently, CGD patients suffer from two clinical manifestations: recurrent, life-threatening bacterial and fungal infections and excessive inflammatory reactions leading to granulomatous lesions. Although the genotype of CGD was linked to the phenotypic expression of the disease, this connection is still controversial and poorly understood. Certain correlations were reported, but the clinical expression of the disease is usually unpredictable, regardless of the pattern of inheritance. CGD mainly affects the lungs, lymph nodes, skin, GI tract and liver. Patients are particularly susceptible to catalase-positive microorganisms, including Staphyloccocus aureus, Nocardia spp. and Gram-negative bacteria, such as Serratia marcescens, Burkholderia cepacea and Salmonella spp. Unusually, catalase-negative microorganisms were reported as well. New antibacterial and antimycotic agents considerably improved the prognosis of CGD. Therapy with IFN-γ is still controversial. Bone marrow stem cell transplantation is currently the only curative treatment and gene therapy needs further development. In this article, the authors discuss the genetic, functional and molecular aspects of CGD and their impact on the clinical expression, infectious complications and the hyperinflammatory state.
authors.affiliation: Pediatric Intensive Care Unit, Meir Medical Center, Kfar Saba, Israel.
authors.forename: Josef
authors.initials: J
authors.lastname: Ben-Ari
authors.forename: Ofir
authors.initials: O
authors.lastname: Wolach
authors.forename: Ronit
authors.initials: R
authors.lastname: Gavrieli
authors.forename: Baruch
authors.initials: B
authors.lastname: Wolach
mesh_terms: D001230:Aspergillus / Q000472:pathogenicity; D001424:Bacterial Infections / Q000150:complications / Q000382:microbiology / Q000473:pathology*; D016026:Bone Marrow Transplantation; D002374:Catalase / Q000378:metabolism; D041321:Chromosomes, Human, X / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006105:Granulomatous Disease, Chronic / Q000150:complications* / Q000188:drug therapy / Q000235:genetics / Q000382:microbiology*; D006801:Humans; D009181:Mycoses / Q000150:complications / Q000382:microbiology / Q000473:pathology; D019255:NADPH Oxidases / Q000378:metabolism; D010641:Phenotype; D017382:Reactive Oxygen Species / Q000378:metabolism; D013211:Staphylococcus aureus / Q000201:enzymology / Q000472:pathogenicity; D016019:Survival Analysis
chemical_list: D017382:Reactive Oxygen Species; D002374:Catalase; D019255:NADPH Oxidases