Chronic granulomatous disease
Open accessAbstract
INTRODUCTION: Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by recurrent, life-threatening bacterial and fungal infections of the skin, the airways, the lymph nodes, the liver, the brain and the bones. Frequently found pathogens are Staphylococcus aureus, Aspergillus species, Klebsiella species, Burkholderia cepacia, Serratia marcescens and Salmonella species. SOURCES OF DATA: CGD is a rare (∼1:250 000 individuals) disease caused by mutations in any one of the five components of the NADPH oxidase in phagocytic leucocytes. This enzyme generates superoxide and is essential for intracellular killing of pathogens by phagocytes. AREAS OF AGREEMENT: CGD patients suffer not only from life-threatening infections, but also from excessive inflammatory reactions. AREAS OF CONTROVERSY: Neither the cause of these inflammatory reactions nor the way to treat them is clear. AREAS TIMELY FOR DEVELOPING RESEARCH: Patient selection for and timing of bone marrow transplantation along with gene therapy.
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Patients lacking functional NADPH oxidase are more susceptible to microbial infections.
“Individuals with CGD have persistent bacterial and fungal infections due to defects in NOx [94].”
From The Role of Reactive Species on Innate Immunity (2022) · cites this paper as [94]
NADPH oxidase NOx, as an •O2− producer, is essential for microbial destruction.
“NADPH oxidase NOx, as an •O2− producer is essential for microbial destruction, and patients lacking this functional oxidase are more susceptible to microbial infections.”
From The Role of Reactive Species on Innate Immunity (2022) · cites this paper as [94]
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Inherited p40phox deficiency differs from classic chronic granulomatous disease
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“The second component is a cytosolic heterotrimer composed of p40phox, p47phox, and p67phox, which form the regulatory part of the NADPH oxidase and are encoded by NCF4, NCF1, and NCF2, respectively (22).”
Self-citationThe Role of Reactive Species on Innate Immunity
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Metformin inhibits ROS production by human M2 macrophages via the activation of AMPK
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Oxidants in Physiological Processes
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“The vital importance of this enzyme is illustrated by a human genetic disorder called chronic granulomatous disease (CGD), which is a primary immunodeficiency disorder caused by defects in one of the NOX subunits and characterized by severe and recurrent life-threatening infections (140).”
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Considerations in the Diagnosis of Chronic Granulomatous Disease
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Beyond the Extra Respiration of Phagocytosis: NADPH Oxidase 2 in Adaptive Immunity and Inflammation
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Cell-autonomous immunity by IFN-induced GBPs in animals and plants
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Vitamin C and Neutrophil Function: Findings from Randomized Controlled Trials
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Self-citationRaising the ‘Good’ Oxidants for Immune Protection
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Chronic Granulomatous Disease (CGD): Commonly Associated Pathogens, Diagnosis and Treatment
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“…and histiocytes evolve and arrange to form granulomas, one of the hallmarks of CGD, provoking diverse clinical manifestations of obstruction such as delayed gastric emptying, antral narrowing of the stomach, dysphagia, emesis, weight loss, biliary tract or gastrointestinal obstruction [13].”
Regulation of Virulence by Two-Component Systems in Pathogenic Burkholderia
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Gene therapy and genome editing for primary immunodeficiency diseases
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Cellular Therapies in Chronic Granulomatous Disease
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Programmed ageing: decline of stem cell renewal, immunosenescence, and Alzheimer's disease
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“They are also essential: deficiency in ROS production (chronic granulomatous disease, CGD) is characterised by immunodeficiency, severe recurrent infections, and early mortality (Kuhns et al., 2010; Roos, 2016): only 50% reach the age of 30 years, and survival in others is stratified according to the amount of residua…”
Old Dogs, New Tricks: New Insights into the Iron/Manganese Superoxide Dismutase Family
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Application of Flow Cytometry in Primary Immunodeficiencies: Experience From India
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Killing three birds with one BPI: Bactericidal, opsonic, and anti-inflammatory functions
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Severe hematopoietic stem cell inflammation compromises chronic granulomatous disease gene therapy
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“The regulatory part is a cytosolic heterotrimer composed of p40, p47, and p67, encoded respectively by NCF4, NCF1, andNCF2.(4) Following phagocyte activation, the NADPH oxidase”
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Reactive Oxygen Species in Acute Lymphoblastic Leukaemia: Reducing Radicals to Refine Responses
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Germline Variants of CYBA and TRPM4 Predispose to Familial Colorectal Cancer
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“Patients suffer from life-threatening infections and from excessive inflammatory reactions [41].”
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High Levels of IL-18 and IFN-γ in Chronically Inflamed Tissue in Chronic Granulomatous Disease
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Very early onset IBD: novel genetic aetiologies
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“About 70% of the CGD patients are males carrying hemizygous LOF mutations in CYBB; 20 and 5% carry LOF recessive mutations in the autosomal genes NCF1 and NCF2, respectively.(79,80) Mutations in NCF4 are rarer and manifest with peripheral rather than invasive infections and with inflammatory lesions of the skin and ga…”
Primary Immunodeficiency Diseases
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Major CD4 T-Cell Depletion and Immune Senescence in a Patient with Chronic Granulomatous Disease
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Self-citationChallenging Mimickers in the Diagnosis of Sarcoidosis: A Case Study
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Chronic Granulomatous Disease First Diagnosed in Adulthood Presenting With Spinal Cord Infection
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Self-citationDe novo DUOX2 expression in neutrophil subsets shapes the pathogenesis of intestinal disease
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Chronic Granulomatous Disease in children: a single center experience
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“Interestingly, patients with X-linked chronic granulomatous disease (CGD) (gp91phox deficiency) share biological properties such as low p65 phosphorylation, defective ROS production, and high inflammasome activity with our p.R157X cases [36].”
InfluentialRegulation of Derlin-1-mediated degradation of NADPH oxidase partner p22 by thiol modification
Miyano, K., Okamoto, S., Kajikawa, M., Kiyohara, T., Kawai, C., 山内, 明., & Kuribayashi, F. (2022) · Redox Biology · doi:10.1016/j.redox.2022.102479 · Cited by 9 · see citing works
“Genetic defects in Nox2 (encoded by the X-linked CYBB gene) lead to chronic granulomatous disease (CGD), which is characterized by recurrent life-threatening bacterial and fungal infections [9].”
Miyano, K., Okamoto, S., 山内, 明., Kajikawa, M., Kiyohara, T., Taura, M., Kawai, C., & Kuribayashi, F. (2020) · Free Radical Research · doi:10.1080/10715762.2020.1823383 · Cited by 9 · see citing works
Chronic granulomatous disease caused by maternal uniparental isodisomy of chromosome 16
García‐Morato, M. B., Nevado, J. B., González‐Granado, L. I., Urgellés, A. S., Pena, R. R., & Cerdán, A. F. (2017) · The Journal of Allergy and Clinical Immunology In Practice · doi:10.1016/j.jaip.2017.01.018 · Cited by 9 · see citing works
Evolution towards Virulence in a Burkholderia Two-Component System
Schaefers, M. M., Wang, B. X., Boisvert, N. M., Martini, S. J., Bonney, S. L., Marshall, C. W., Laub, M. T., Cooper, V. S., & Priebe, G. P. (2021) · mBio · doi:10.1128/mbio.01823-21 · Cited by 8 · see citing works
- Authors
- Roos, D.
- Affiliations
- Amsterdam UMC Location University of Amsterdam (NL)
- Corresponding author
- Roos, Dirk
- ORCID
- Roos, Dirk
- Venue
- British Medical Bulletin
- Publisher
- Oxford University Press (OUP)
- Published
- 2016-03-16
- Volume
- 118
- Issue
- 1
- Pages
- 50-63
- ISSN
- 0007-1420 (ISSN-L)
- 1471-8391
- PMC
- PMC5127417
- OpenAlex
- W2305820599
- Cited by
- 212
- References
- 76
- Citations by year
- 2026: 9 · 2025: 17 · 2024: 16 · 2023: 20 · 2022: 19 · 2021: 30 · 2020: 25 · 2019: 30 · 2018: 21 · 2017: 18 · 2016: 4 · 2015: 2 · 2014: 1
- FWCI
- 2.34
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- British Medical Bulletin (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunodeficiency and Autoimmune Disorders
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Blood disorders and treatments
- Keywords
- chronic granulomatous disease, primary immunodeficiency, NADPH oxidase, superoxide, phagocytes, bacterial and fungal infections, Staphylococcus aureus, Aspergillus, Burkholderia cepacia, Klebsiella, Serratia marcescens, Salmonella, inflammation, bone marrow transplantation, gene therapy
- MeSH terms
- Bacterial Infections, Granulomatous Disease, Chronic, Humans, Mutation, Mycoses, Phagocytes, Genetic Therapy, Bone Marrow Transplantation, NADPH Oxidases, Genetic Predisposition to Disease, Molecular Diagnostic Techniques
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