Chronic Granulomatous Disease: The European Experience

By J. M. van den Berg, Elsbeth van Koppen, A. Åhlin, B. H. Belohradsky, E. Bernatowska, L. Corbeel, T. Español, A. Fischer, M. Kurenko-Deptuch, R. Mouy and 9 more. PLoS ONE, 2009

686 citations recorded by the source corpus.

CGD is an immunodeficiency caused by deletions or mutations in genes that encode subunits of the leukocyte NADPH oxidase complex. Normally, assembly of the NADPH oxidase complex in phagosomes of certain phagocytic cells leads to a “respiratory burst”, essential for the clearance of phagocytosed micro-organisms. CGD patients lack this mechanism, which leads to life-threatening infections and granuloma formation. However, a clear picture of the clinical course of CGD is hampered by its low prevalence (∼1∶250,000). Therefore, extensive clinical data from 429 European patients were collected and analyzed. Of these patients 351 were males and 78 were females. X-linked (XL) CGD (gp91phox deficient) accounted for 67% of the cases, autosomal recessive (AR) inheritance for 33%. AR-CGD was diagnosed later in life, and the mean survival time was significantly better in AR patients (49.6 years) than in XL CGD (37.8 years), suggesting a milder disease course in AR patients. The disease manifested itself most frequently in the lungs (66% of patients), skin (53%), lymph nodes (50%), gastrointestinal tract (48%) and liver (32%). The most frequently cultured micro-organisms per episode were Staphylococcus aureus (30%), Aspergillus spp. (26%), and Salmonella spp. (16%). Surprisingly, Pseudomonas spp. (2%) and Burkholderia cepacia (<1%) were found only sporadically. Lesions induced by inoculation with BCG occurred in 8% of the patients. Only 71% of the patients received antibiotic maintenance therapy, and 53% antifungal prophylaxis. 33% were treated with γ-interferon. 24 patients (6%) had received a stem cell transplantation. The most prominent reason of death was pneumonia and pulmonary abscess (18/84 cases), septicemia (16/84) and brain abscess (4/84). These data provide further insight in the clinical course of CGD in Europe and hopefully can help to increase awareness and optimize the treatment of these patients.

Subfields: Immunology, Infectious Diseases, Physiology

View Paper: https://www.semanticscholar.org/paper/05b1889c904e8d6261b583daeec64de72df3d0d8

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

Citations in the corpus

The Diagnostic Approach to Monogenic Very Early Onset Inflammatory Bowel Disease (2014, neutral): “Findings from initial genome-wide pediatric association studies focused on adolescents and confirm a polygenic model.(27,28) There are no well-powered genome-wide association studies of patients with EOIBD or VEOIBD.”
2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. (2014, background): “Patients with CGD are not at increased risk for infections with pneumococcus [127, 128], and there is limited data on the risk of invasive pneumococcal infection in patients with other phagocytic cell defects [127, 128].”
Dying for a cause: NETosis, mechanisms behind an antimicrobial cell death modality (2011, positive): “recurrent life-threatening infections by a narrow set of microorganisms.(11) We recently found that formation of NETs by activated neutrophils requires not only NADPH-oxidasemediated superoxide production, but also autophagy.”
Neutrophils to the ROScue: Mechanisms of NADPH Oxidase Activation and Bacterial Resistance (2017, background): “…of phagocytes to mount a respiratory burst, the majority of CGD patients are susceptible to recurrent and lifethreatening bacterial and fungal infections early in childhood, due to ineffective killing and containment of the pathogens (van den Berg et al., 2009; Holland, 2013; O’Neill et al., 2015).”
2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. (2014, background): “Patients with CGD are not at increased risk for infections with pneumococcus [127, 128], and there is limited data on the risk of invasive pneumococcal infection in patients with other phagocytic cell defects [127, 128].”