Mycobacterial disease in patients with chronic granulomatous disease: A retrospective analysis of 71 cases

Conti, Francesca; Reyes, Saúl Oswaldo Lugo; Galicia, Lizbeth Blancas; He, Jianxin; Aksu, Güzide; Oliveira, Edgar Borges de; Deswarte, Caroline; Hubeau, Marjorie; Karaca, Neslihan Edeer; Suremain, Maylis de; Guérin, Antoine; Baba, Laila Ait; Prando, Carolina; Guerrero, G. G.; Emiroğlu, Melike; Öz, Fatma Nur; Nakashimada, Marco Antonio Yamazaki; Serrano, Edith; Espinosa, Sara; Barlan, Işıl; Pérez, Nicolas; Regairaz, Lorena; Morales, Héctor Eduardo Guidos; Bezrodnik, Liliana; Giovanni, Daniela Di; Dbaibo, Ghassan; Ailal, Fatima; Galicchio, Miguel; Oleastro, Matías; Chemli, J.; Danielian, Silvia; Pérez, Laura; Ortega, María Claudia; Lavin, Susana Soto; Hertecant, Joseph; Anal, Özden; Kechout, Nadia; Al-Idrissi, Eman; ElGhazali, Gehad; Бондаренко, Анастасія; Chernyshova, Liudmyla; Čižnár, Peter; Herbigneaux, Rose-Marie; Diabate, Aminata; Ndaga, Stéphanie; Konte, Barik; Czarna, Ambre; Migaud, Mélanie; Pedraza-Sánchez, Sigifredo; Zaidi, Mussaret B.; Vogt, Guillaume; Blanche, Stéphane; Ben‐Mustapha, Imen; Mansouri, Davood; Abel, Laurent; Boisson–Dupuis, Stéphanie; Mahlaoui, Nizar; Bousfiha, Ahmed Aziz; Pïcard, Capucine; Barbouche, Ridha; Al‐Muhsen, Saleh; Espinosa-Rosales, Francisco; Kütükçüler, Necil; Condino‐Neto, Antônio; Casanova, Jean‐Laurent; Bustamante, Jacinta

doi:10.1016/j.jaci.2015.11.041

Cited by 111 publications

(92 citation statements)

References 51 publications

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“…However, to our knowledge, no patient with CGD has ever been reported to suffer from this fungal disease. This situation is reminiscent of that of tuberculosis, which is actually much more common than initially thought in CGD patients living in areas of endemic disease (49). Its pathogenesis has been attributed to defects of NADPH oxidase activity in mononuclear phagocytes (25).…”

Section: Discussionmentioning

confidence: 95%

Inherited p40phox deficiency differs from classic chronic granulomatous disease

Geer¹,

Nieto-Patlán²,

Kuhns³

et al. 2018

Journal of Clinical Investigation

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100

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Biallelic loss-of-function (LOF) mutations of the NCF4 gene, encoding the p40 phox subunit of the phagocyte NADPH oxidase, have been described in only 1 patient. We report on 24 p40 phox -deficient patients from 12 additional families in 8 countries. These patients display 8 different in-frame or out-of-frame mutations of NCF4 that are homozygous in 11 of the families and compound heterozygous in another. When overexpressed in NB4 neutrophil-like cells and EBV-transformed B cells in vitro, the mutant alleles were found to be LOF, with the exception of the p.R58C and c.120_134del alleles, which were hypomorphic. Particle-induced NADPH oxidase activity was severely impaired in the patients' neutrophils, whereas PMAinduced dihydrorhodamine-1,2,3 (DHR) oxidation, which is widely used as a diagnostic test for chronic granulomatous disease (CGD), was normal or mildly impaired in the patients. Moreover, the NADPH oxidase activity of EBV-transformed B cells was also severely impaired, whereas that of mononuclear phagocytes was normal. Finally, the killing of Candida albicans and Aspergillus fumigatus hyphae by neutrophils was conserved in these patients, unlike in patients with CGD. The patients suffer from hyperinflammation and peripheral infections, but they do not have any of the invasive bacterial or fungal infections seen in CGD. Inherited p40 phox deficiency underlies a distinctive condition, resembling a mild, atypical form of CGD. phox -deficient patient is compound heterozygous for a premature stop codon and a missense mutation in the PX domain that compromises binding to PI(3)P, which results in the impairment of neutrophil phagocytosis-induced oxidase activity (26). As in classic CGD neutrophils, intracellular oxidant production after stimulation with serum-opsonized zymosan (SOZ), IgG beads, or serumopsonized Staphylococcus aureus is impaired in the patient's neutrophils, and S. aureus killing is also defective (20,26,30). However, in this patient, unlike in classic CGD patients, the production of O 2 -by neutrophils in response to stimulation with PMA or formyl-methionyl-leucyl-phenylalanine (fMLF) is normal (26). The killing of S. aureus by neutrophils is also impaired in p40 phox deficiency and classic CGD are largely unknown. Here, we describe the characteristics of 24 patients from 12 families in 8 countries with biallelic mutations of NCF4. The Journal of Clinical Investigation R E S E A R C H A R T I C L E

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Section: Discussionmentioning

confidence: 95%

Inherited p40phox deficiency differs from classic chronic granulomatous disease

Geer¹,

Nieto-Patlán²,

Kuhns³

et al. 2018

Journal of Clinical Investigation

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100

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“…In many immune deficiencies, the definite treatment is stem cell transplantation, which is lifesaving (29). Stem cell transplantation was performed in 36% of our patients.…”

Section: Discussionmentioning

confidence: 97%

Frequency of Mycobacterium bovis and mycobacteria in primary immunodeficiencies

Severcan¹,

Karaca²,

Aksu³

et al. 2017

Turk Pediatri Ars

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Aim: Susceptibility to mycobacterial diseases is observed in some primary immunodeficiency diseases. In this study, we aimed to evaluate mycobacterial infections in primary immunodeficiency diseases. Material and Methods:Patients under follow-up by Ege University Pediatric Immunology Department for severe combined and combined immunodeficiencies, interleukin 12/ interferon gamma receptor deficiency, nuclear factor kappa-beta essential modulator deficiency and chronic granulomatosis disease were evaluated retrospectively in terms of the frequency and characteristics of mycobacterial infections using a questionnaire form for demographic properties, clinical features and laboratory tests. Results: A diagnosis of mycobacterial infection was made clinically in a total of 25 patients including five (11.3%) of 45 patients who had severe combined immune deficiency, 12 (52.3%) of 21 patients who had chronic granulomatous disease, four patients (100%) who had interferon gamma receptor 2 partical deficiency, two patients (100%) who had interleukin 12 receptor beta 1 deficiency and one patient (100%) who had nuclear factor kapa-beta essential modulator deficiency. Mycobacterium strain could be typed in 14 (33%) of these 25 patients including Mycobacterium bovis, Mycobacterium chelonea, Mycobacterium elephantis, Mycobacterium fortuitum, and Mycobacterium tuberculosis. All patients were treated with anti-tuberculosis therapy. Thirty-six percent of these 25 patients underwent hematopoietic stem cell transplantation. Eight patients (five before, three after transplantation) died. Conclusions: Non-tuberculosis mycobacteria including mainly Mycobacterium bovis were observed with a higher rate compared to Mycobacterium tuberculosis in primary immunodeficiencies, especially in those affecting the interleukin 12/interferon gamma pathway. Early diagnosis of primary immunodeficiencies with neonatal screening program and preventing administration of the Bacille Calmette-Guerin vaccine in these patients is important.

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“…The unresponsiveness of infant AMφs to IFNγ might be caused by their lack of exposure to viral infections, which have been shown to drive training and "innate macrophage memory" through CD8+ T cell-mediated priming of AMφs by IFNγ (4). Infant AMφs also exhibited lower expression of the IFNγ-stimulated gene (ISG) CYBB, which encodes a membrane-bound subunit of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase system responsible for ROS production, mutations of which are associated with susceptibility to mycobacterial infection (34). In addition, infant AMφs exhibited lower expression of genes involved in antimycobacterial phagosome maturation (DRAM2 and UVRAG) that are not known to be ISGs (35).…”

Section: Discussionmentioning

confidence: 99%

Infant Alveolar Macrophages Are Unable to Effectively Contain Mycobacterium tuberculosis

et al. 2020

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Infants are more likely to develop lethal disseminated forms of tuberculosis compared with older children and adults. The reasons for this are currently unknown. In this study we test the hypothesis that antimycobacterial function is impaired in infant alveolar macrophages (AMφs) compared with those of adults. We develop a method of obtaining AMφs from healthy infants using rigid bronchoscopy and incubate the AMφs with live virulent Mycobacterium tuberculosis (Mtb). Infant AMφs are less able to restrict Mtb replication compared with adult AMφs, despite having similar phagocytic capacity and immunophenotype. RNA-Seq showed that infant AMφs exhibit lower expression of genes involved in mycobactericidal activity and IFNγ-induction pathways. Infant AMφs also exhibit lower expression of genes encoding mononuclear cell chemokines such as CXCL9. Our data indicates that failure of AMφs to contain Mtb and recruit additional mononuclear cells to the site of infection helps to explain the more fulminant course of tuberculosis in early life.

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Mycobacterial disease in patients with chronic granulomatous disease: A retrospective analysis of 71 cases

Cited by 111 publications

References 51 publications

Inherited p40phox deficiency differs from classic chronic granulomatous disease

Inherited p40phox deficiency differs from classic chronic granulomatous disease

Frequency of Mycobacterium bovis and mycobacteria in primary immunodeficiencies

Infant Alveolar Macrophages Are Unable to Effectively Contain Mycobacterium tuberculosis

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