scholarly journals Virulence and Cellular Interactions of Burkholderia multivorans in Chronic Granulomatous Disease

2009 ◽  
Vol 77 (10) ◽  
pp. 4337-4344 ◽  
Author(s):  
Adrian M. Zelazny ◽  
Li Ding ◽  
Houda Z. Elloumi ◽  
Lauren R. Brinster ◽  
Fran Benedetti ◽  
...  
Keyword(s):  
Chronic Granulomatous Disease ◽  
Burkholderia Cepacia ◽  
Cell Entry ◽  
Cellular Interactions ◽  
Granulomatous Disease ◽  
Burkholderia Multivorans ◽  
Healthy Donors ◽  
Cell Association ◽  
Life Threatening ◽  
Shed Light

ABSTRACT Chronic granulomatous disease (CGD) patients are susceptible to life-threatening infections by the Burkholderia cepacia complex. We used leukocytes from CGD and healthy donors and compared cell association, invasion, and cytokine induction by Burkholderia multivorans strains. A CGD isolate, CGD1, showed higher cell association than that of an environmental isolate, Env1, which correlated with cell entry. All B. multivorans strains associated significantly more with cells from CGD patients than with those from healthy donors. Similar findings were observed with another CGD pathogen, Serratia marcescens, but not with Escherichia coli. In a mouse model of CGD, strain CGD1 was virulent while Env1 was avirulent. B. multivorans organisms were found in the spleens of CGD1-infected mice at levels that were 1,000 times higher than those found in Env1-infected mice, which was coincident with higher levels of the proinflammatory cytokine interleukin-1β. Taken together, these results may shed light on the unique susceptibility of CGD patients to specific pathogens.

scholarly journals Xanthine Oxidase Contributes to Host Defense against Burkholderia cepacia in the p47phox−/− Mouse Model of Chronic Granulomatous Disease

2000 ◽  
Vol 68 (4) ◽  
pp. 2374-2378 ◽  
Author(s):  
Brahm H. Segal ◽  
Nobuaki Sakamoto ◽  
Mayur Patel ◽  
Kosei Maemura ◽  
Andrew S. Klein ◽  
...  
Keyword(s):  
Mouse Model ◽  
Chronic Granulomatous Disease ◽  
Xanthine Oxidase ◽  
Host Defense ◽  
Burkholderia Cepacia ◽  
Fungal Infections ◽  
Granulomatous Disease ◽  
Life Threatening ◽  
Reactive Oxidant ◽  
Reactive Oxidants

ABSTRACT Chronic granulomatous disease (CGD) is an inherited disorder of the NADPH oxidase in which phagocytes are defective in generating superoxide and downstream microbicidal reactive oxidants, leading to recurrent life-threatening bacterial and fungal infections. Xanthine oxidase (XO) is another enzyme known to produce superoxide in many tissues. Using the p47 phox−/− mouse model of CGD, we evaluated the residual antibacterial activity of XO. Clearance of Burkholderia cepacia, a major pathogen in CGD, was reduced in p47 phox−/− mice compared to that in wild-type mice and was further inhibited in p47 phox−/− mice by pretreatment with the specific XO inhibitor allopurinol. Hepatic B. cepaciaburden was similar in the two genotypes, but allopurinol significantly reduced net hepatic killing and killing efficiency only in p47 phox−/− mice. Clearance and killing of intravenous Escherichia coli was intact in p47 phox−/− mice and was unaffected by pretreatment with allopurinol. In CGD, XO may contribute to host defense against a subset of reactive oxidant-sensitive pathogens.

scholarly journals The p47phox mouse knock-out model of chronic granulomatous disease.

1995 ◽  
Vol 182 (3) ◽  
pp. 751-758 ◽  
Author(s):  
S H Jackson ◽  
J I Gallin ◽  
S M Holland
Keyword(s):  
Nadph Oxidase ◽  
Chronic Granulomatous Disease ◽  
Fungal Infections ◽  
Critical Role ◽  
Granulomatous Inflammation ◽  
Mammalian Host ◽  
Granulomatous Disease ◽  
Knock Out ◽  
Phagocyte Nadph Oxidase ◽  
Life Threatening

Chronic granulomatous disease (CGD) is caused by a congenital defect in phagocyte reduced nicotinamide dinucleotide phosphate (NADPH) oxidase production of superoxide and related species. It is characterized by recurrent life-threatening bacterial and fungal infections and tissue granuloma formation. We have created a mouse model of CGD by targeted disruption of p47phox, one of the genes in which mutations cause human CGD. Identical to the case in human CGD, leukocytes from p47phox-/- mice produced no superoxide and killed staphylococci ineffectively. p47phox-/- mice developed lethal infections and granulomatous inflammation similar to those encountered in human CGD patients. This model mirrors human CGD and confirms a critical role for the phagocyte NADPH oxidase in mammalian host defense.

NORMAL GRANULOCYTE INFUSION THERAPY FOR ASPERGILLOSIS IN CHRONIC GRANULOMATOUS DISEASE

PEDIATRICS ◽  
1973 ◽  
Vol 51 (2) ◽  
pp. 230-233
Author(s):  
Andrew A. Raubitschek ◽  
Alan S. Levin ◽  
Daniel P. Stites ◽  
Edward B. Shaw ◽  
H. Hugh Fudenberg
Keyword(s):  
Adverse Effects ◽  
Chronic Granulomatous Disease ◽  
Blood Cells ◽  
White Blood Cells ◽  
Infusion Therapy ◽  
Granulomatous Disease ◽  
Transient Improvement ◽  
Life Threatening ◽  
Granulocyte Function

An 8-year-old boy with chronic granulomatous disease (CGD) was admitted in moribund condition with aspergillus pneumonia. Because of the gravity of the situation, normal granulocyte infusions were used as adjuncts to the more conventional antimicrobial therapy. White blood cells, derived from a total of 58 units of whole blood obtained by leukophoresis of the father, were given in two separate doses. The first dose, totaling 2.8 x 1010 granulocytes, was coincident with significant improvement, and the second, totaling 3.0 x 1010 granulocytes, was coincident with the onset of clinical improvement and interim recovery. Transient improvement in in vitro granulocyte function was noted in cells taken from the patient's blood immediately after infusion. No adverse effects of the infusions were noted in either the patient or the donor. Although it is impossible to divorce the therapeutic effect of the granulocyte infusions from the more conventional therapy, we conclude that normal granulocyte infusions can be considered a valid adjunct in children with CGD who are suffering from a life-threatening infection.

scholarly journals Macrophage activation syndrome/haemophagocytic lymphohistiocytosis secondary to Burkholderia cepacia complex septicaemia in an elderly female carrier of X-linked chronic granulomatous disease with extreme lyonisation: ‘cepacia syndrome’ revisited

2019 ◽  
Vol 12 (8) ◽  
pp. e230434 ◽  
Author(s):  
Nicolás Urriola ◽  
Andrew Williams ◽  
Karuna Keat
Keyword(s):  
Chronic Granulomatous Disease ◽  
Burkholderia Cepacia ◽  
Macrophage Activation Syndrome ◽  
Macrophage Activation ◽  
Burkholderia Cepacia Complex ◽  
Female Carrier ◽  
Granulomatous Disease ◽  
Haemophagocytic Lymphohistiocytosis ◽  
Stimulating Factor ◽  
Activation Syndrome

X-linked carriers of chronic granulomatous disease (CGD) may become phenotypically affected if substantial skewing from lyonisation occurs. We describe a 73-year-old female carrier with an overt CGD phenotype due to skewed lyonisation, complicated by macrophage activation syndrome (MAS)/haemophagocytic lymphohistiocytosis (HLH) secondary to Burkholderiacepacia complex septicaemia that was successfully treated with a combination of three antibiotics, an antifungal, granulocyte colony stimulating factor, intravenous immune globulin (IVIG) and ciclosporin. Fully phenotypic immunodeficiency is possible in X-linked CGD carriers when skewed lyonisation occurs, rendering such patients to all the same sequelae of CGD such as MAS/HLH. MAS/HLH should be thoroughly excluded when evaluating ‘cepacia syndrome’ in non-CGD patients.

scholarly journals An Uncommon Feature of Chronic Granulomatous Disease in a Neonate

2016 ◽  
Vol 2016 ◽  
pp. 1-4 ◽  
Author(s):  
Razieh Afrough ◽  
Sayyed Shahabeddin Mohseni ◽  
Setareh Sagheb
Keyword(s):  
Mortality Rate ◽  
Chronic Granulomatous Disease ◽  
High Mortality ◽  
Neonatal Period ◽  
Fungal Infections ◽  
Granuloma Formation ◽  
Granulomatous Disease ◽  
Life Threatening

Chronic Granulomatous Disease (CGD) represents recurrent life-threatening bacterial and fungal infections and granuloma formation with a high mortality rate. CGD’s sign and symptoms usually appear in infancy and children before the age of five; therefore, its presentation in neonatal period with some uncommon features may be easily overlooked. Here we describe a case of CGD in a 24-day-old boy, presenting with a diffuse purulent vesiculopustular rash and multiple osteomyelitis.

scholarly journals Atypical presentation of chronic granulomatous disease with Burkholderia cepacia

2014 ◽  
Vol 2014 (aug06 1) ◽  
pp. bcr2013201524-bcr2013201524 ◽  
Author(s):  
M. Vining ◽  
N. Sharma ◽  
M. Guill
Keyword(s):  
Chronic Granulomatous Disease ◽  
Burkholderia Cepacia ◽  
Atypical Presentation ◽  
Granulomatous Disease

scholarly journals Case Report: Secondary Hemophagocytic Lymphohistiocytosis With Disseminated Infection in Chronic Granulomatous Disease—A Serious Cause of Mortality

2020 ◽  
Vol 11 ◽  
Author(s):  
Jacqueline D. Squire ◽  
Stephanie N. Vazquez ◽  
Angela Chan ◽  
Michele E. Smith ◽  
Deepak Chellapandian ◽  
...  
Keyword(s):  
Immune Deficiency ◽  
Chronic Granulomatous Disease ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Fungal Infections ◽  
Primary Immune Deficiency ◽  
Granulomatous Disease ◽  
Simultaneous Treatment ◽  
Hematopoietic Stem ◽  
Increased Risk ◽  
Life Threatening

Chronic granulomatous disease (CGD) is a primary immune deficiency due to defects in phagocyte respiratory burst leading to severe and life-threatening infections. Patients with CGD also suffer from disorders of inflammation and immune dysregulation including colitis and granulomatous lung disease, among others. Additionally, patients with CGD may be at increased risk of systemic inflammatory disorders such as hemophagocytic lymphohistiocytosis (HLH). The presentation of HLH often overlaps with symptoms of systemic inflammatory response syndrome (SIRS) or sepsis and therefore can be difficult to identify, especially in patients with a primary immune deficiency in which incidence of infection is increased. Thorough evaluation and empiric treatment for bacterial and fungal infections is necessary as HLH in CGD is almost always secondary to infection. Simultaneous treatment of infection with anti-microbials and inflammation with immunosuppression may be needed to blunt the hyperinflammatory response in secondary HLH. Herein, we present a series of X-linked CGD patients who developed HLH secondary to or with concurrent disseminated CGD-related infection. In two patients, CGD was a known diagnosis prior to development of HLH and in the other two CGD was diagnosed as part of the evaluation for HLH. Concurrent infection and HLH were fatal in three; one case was successfully treated, ultimately receiving hematopoietic stem cell transplantation. The current literature on presentation, diagnosis, and treatment of HLH in CGD is reviewed.

Hemophagocytic Syndrome and Burkholderia cepacia Splenic Microabscesses in a Child With Chronic Granulomatous Disease

2004 ◽  
Vol 23 (9) ◽  
pp. 882-884 ◽  
Author(s):  
Sayomporn Sirinavin ◽  
Chonnamet Techasaensiri ◽  
Samart Pakakasama ◽  
Malai Vorachit ◽  
Rattanaporn Pornkul ◽  
...  
Keyword(s):  
Chronic Granulomatous Disease ◽  
Burkholderia Cepacia ◽  
Hemophagocytic Syndrome ◽  
Granulomatous Disease

Retroviral Gene Therapy for X-Linked Chronic Granulomatous Disease: Results from Phase I/II Trial.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2349-2349 ◽  
Author(s):  
Joong Gon Kim ◽  
Hyo Seop Ahn ◽  
Hyoung Jin Kang ◽  
Sujeong Kim ◽  
Youngtae Hong ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Nadph Oxidase ◽  
Phase I ◽  
Chronic Granulomatous Disease ◽  
Viral Vectors ◽  
Conditioning Regimen ◽  
Transduction Efficiency ◽  
Granulomatous Disease ◽  
Gene Therapy Trial ◽  
Life Threatening

Abstract X-linked chronic granulomatous disease (X-CGD) is an inherited immunodeficiency disease caused by a defect in the gp91phox gene encoding one of the subunits of the NADPH oxidase complex. NADPH oxidase plays an important role in eradicating the pathogen engulfed by the phagocytes. Therefore, CGD patients suffer from recurring life-threatening infection by bacteria or fungi, and die before 30 in most cases. In an effort to treat this life-threatening disease, we initiated a phase I/II gene therapy trial in 2007. Two X-CGD patients were enrolled in the trial. The retroviral vector used for gene delivery was the MLV-based MT vector containing gp91 phox cDNA (Yu et al., Gene Ther2000; 7: 797, Hong et al., J Gene Med2004; 6: 724). Viral vectors have been produced from PG13 packaging cells in compliance with GMP. The clinical protocol was approved by the Korean FDA. G-CSF mobilized peripheral blood CD34+ cells were obtained from patients, and transduced in retronectin-coated gas-permeable bags containing SCGM media supplemented with SCF, FLT3L, TPO, and IL-3. The transduction efficiency was 10.5% for patient #1 and 28.5% for patient #2 when assessed by gp91 FACS analysis. Before receiving transduced cells, patients were treated with a conditioning regimen consisting of busulfan (3.2 mg/kg/day for 2 days) and fludarabine (40 mg/m2/day for 3 days). No adverse effects were observed from the use of busulfan and fludarabine. The percentage of superoxide-producing cells, as determined by DHR assay, was 6.4% and 14.5% at day 17, and decreased to less than 0.1% (after 1 year) and 0.4% (after 7 months). Thus far, abnormal cell expansion has not been observed.

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