Chronic granulomatous disease (CGD) was first described in the 1950s and has become a paradigm for genetic neutrophil diseases. It is characterized by recurrent infections with a narrow spectrum of bacteria and fungi as well as a common set of inflammatory complications most notably including inflammatory bowel disease. Over the last half century major advances in management have profoundly altered the major clinical issues and the life expectancy of CGD. With X-linked and autosomal recessive forms, it has been an important disease for the development of bone marrow transplantation and gene therapy. Some of the recent developments in infectious syndromes, inflammatory complications, and curative approaches are discussed in this review.
Last. Alessandro Aiuti(University of Rome Tor Vergata)H-Index: 68
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Regulated transgene expression may improve the safety and efficacy of hematopoietic stem cell (HSC) gene therapy. Clinical trials for X-linked chronic granulomatous disease (X-CGD) employing gammaretroviral vectors were limited by insertional oncogenesis or lack of persistent engraftment. Our novel strategy, based on regulated lentiviral vectors (LV), targets gp91phox expression to the differentiated myeloid compartment while sparing HSC, to reduce the risk of genotoxicity and potential perturba...
Last. Steven M. Holland(NIH: National Institutes of Health)H-Index: 114
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Background. Chronic granulomatous disease (CGD) is due to defective nicotinamide adenine dinucleotide phosphate oxidase activity and characterized by recurrent infections with a limited spectrum of bacteria and fungi as well as inflammatory complications. To understand the impact of common severe infections in CGD, we examined the records of 268 patients followed at a single center over 4 decades. Methods. All patients had confirmed diagnoses of CGD, and genotype was determined where possible. M...
Chronic granulomatous disease (CGD), a rare inherited disorder of the innate immune system, results from mutations in any one of the five genes encoding the subunits of the nicotinamide adenine dinucleotide phosphate-oxidase (NADPH) oxidase enzyme, and is characterized by recurrent life-threatening bacterial and fungal infections. Molecular analysis of 14 Omani CGD patients from 10 families, diagnosed to have CGD on clinical (recurrent infections) and biochemical grounds (positive for both the n...
Last. Adrian M. Zelazny(NIH: National Institutes of Health)H-Index: 36
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We describe a case of paravertebral abscess caused by a Phellinus sp. in a boy with chronic granulomatous disease. Sequence-based identification of this mold, a new agent of disease, suggests a close relation to Phellinus umbrinellus.
Purpose Chronic granulomatous disease (CGD) is characterized by an inability of phagocytes to produce reactive oxygen species (ROS), which are required to kill some microorganisms. CGD patients are known to suffer from recurrent bacterial and/or fungal infections from the first year of life onwards. From 2009 to 2013, 12 cases of CGD were diagnosed in Morocco. We describe here these Moroccan cases of CGD.
Summary Background In chronic granulomatous disease allogeneic haemopoietic stem-cell transplantation (HSCT) in adolescents and young adults and patients with high-risk disease is complicated by graft-failure, graft-versus-host disease (GVHD), and transplant-related mortality. We examined the effect of a reduced-intensity conditioning regimen designed to enhance myeloid engraftment and reduce organ toxicity in these patients. Methods This prospective study was done at 16 centres in ten countries...
Chronic Granulomatous Disease (CGD), caused by genetic defects in components of the phagocyte NADPH oxidase pathway, leads to recurrent life-threatening bacterial and invasive fungal infections. While a number of unique pathogens have been associated with this disease, the causative organisms may be difficult to identify. Here, we present a 24 year old male with known X-linked CGD who concurrently developed a cervical abscess and an abscess in the subcutaneous tissues of the right hip, both of w...
Inasmuch as neutrophils are the primary cellular defense against bacterial and fungal infections, disorders that affect these white cells typically predispose individuals to severe and recurrent infections. Therefore, diagnosis of such disorders is an important first step in directing long-term treatment/care for the patient. Herein, we describe methods to identify chronic granulomatous disease, leukocyte adhesion deficiency, and neutropenia. The assays are relatively simple to perform and cost ...
Last. Dirk Roos(UvA: University of Amsterdam)H-Index: 114
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Background Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disorder of phagocytes resulting in impaired killing of bacteria and fungi. A mutation in one of the 4 genes encoding the components p22 phox , p47 phox , p67 phox , and p40 phox of the leukocyte nicotinamide dinucleotide phosphate reduced (NADPH) oxidase leads to autosomal recessive (AR) CGD. A mutation in the CYBB gene encoding gp91 phox leads to X-linked recessive CGD. Objective The aim of this study is to show ...
Last. Maria Kanariou(Boston Children's Hospital)H-Index: 20
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Chronic Granulomatous Disease (CGD) is an uncommon primary immunodeficiency caused by the absence or dysfunction of one of NADPH oxidase subunits, with heterogeneous genetic aetiologies. The aim of this study was the CGD patient registry in Greece, the identification of the responsible genotype and the potential correlation with the patient’s clinical phenotype. Medical charts of 24 CGD patients, investigated by NBT test or DHR for NADPH oxidase activity, Western blot analysis for NADPH oxidase ...
Last. Marie José Stasia(Centre Hospitalier Universitaire de Grenoble)H-Index: 23
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Chronic granulomatous disease (CGD) is an immunodeficiency disorder affecting about 1 in 250,000 individuals. CGD patients suffer from severe, recurrent bacterial and fungal infections. The disease is caused by mutations in the genes encoding the components of the leukocyte NADPH oxidase. This enzyme produces superoxide, which is subsequently metabolized to hydrogen peroxide and other reactive oxygen species (ROS). These products are essential for intracellular killing of pathogens by phagocytic...
Clinical disease caused by the agent of tuberculosis, Mycobacterium tuberculosis, and by less virulent mycobacteria, such as bacillus Calmette-Guerin (BCG) vaccines and environmental mycobacteria, can result from inborn errors of immunity (IEIs). IEIs underlie more than 450 conditions, each associated with an impairment of the development and/or function of hematopoietic and/or non-hematopoietic cells involved in host defense. Only a minority of IEIs confer predisposition to mycobacterial diseas...
Abstract null null The deficiency of dead cell clearance is a prominent pathogenic factor in systemic lupus erythematosus (SLE). In this study, the overexpression of miR-210–5p resulted in the accumulation of secondary necrotic cells (SNECs) in macrophages through the reduction of protein degradation. The upreguation of miR-210–5p inhibited NADPH oxidase (NOX) activation, reactive oxygen species (ROS) generation, and SNEC clearance. miR-210–5p overexpression suppressed Sp1 and HSCARG expression,...
Abstract null null Purpose null This study examined whether one night of sleep fragmentation alters circulating leukocyte counts and mitogen-stimulated oxidative burst by leukocytes at rest and in response to an acute bout of vigorous exercise. null null null Methods null In a randomised crossover design, nine healthy men (mean ± SD: age 22 ± 2 years; BMI 24.9 ± 1.9 kg/m2) were exposed to one night of fragmented or uninterrupted sleep before cycling for 45 minutes at 71% ± 4% VO2peak. Finger-tip...
Abstract null null The uncontrol respiratory burst in neutrophils can lead to inflammation and tissue damage. This study investigates the effect and the underlying mechanism of e-viniferin, a lignan from the root of Vitis thunbergii var. thunbergii, inhibits N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP) induced respiratory burst by antagonizing formyl peptide receptor 1 in human neutrophils. Briefly, e-viniferin specifically inhibited fMLP (0.1 μM: formyl peptide receptor 1 agonist or 1 μ...
The repetitive nature and complexity of multiple medically important genes make them intractable to accurate analysis, despite the maturity of short-read sequencing, resulting in a gap in clinical applications of genome sequencing. The Genome in a Bottle Consortium has provided benchmark variant sets, but these excluded some medically relevant genes due to their repetitiveness or polymorphic complexity. In this study, we characterize 273 of these 395 challenging autosomal genes that have multipl...
Knowledge related to the biology of inborn errors of immunity and associated laboratory testing methods continues to expand at a tremendous rate. Despite this, many patients with inborn errors of immunity suffer for prolonged periods of time before identification of their underlying condition, thereby delaying appropriate care. Understanding that test selection and optimal evaluation for patients with recurrent infections or unusual patterns of inflammation can be unclear, we present a document ...
BACKGROUND A retrospective review of clinical manifestations and demographic pattern of patients diagnosed as chronic granulomatous disease (CGD) from 7 hospitals in Malaysia. An analysis of the available database would establish clinical characteristics, diagnoses and outcome including microbiologic pattern. Studying the demography allows us to document the occurrence of CGD amongst multiethnic groups and its geographical distribution for Malaysia. METHODS Data from the Malaysia Primary Immunod...
BACKGROUND Chronic granulomatous disease (CGD) is a rare primary immunodeficiency which can lead to gastrointestinal (GI) complications including inflammatory bowel disease. Radiographic findings in this cohort have not been well described. AIMS To describe the frequency and spectrum of gastrointestinal abnormalities seen on computed tomography (CT) in patients with CGD and determine whether radiography was predictive of endoscopic or histopathologic inflammatory findings. METHODS A retrospectiv...
