Chronic granulomatous disease with markedly elevated IgE levels mimicking hyperimmunoglobulin E syndrome

Patıroğlu, Türkan; Gungor, Hatice; Lazaroski, Sandra; Ünal, Ekrem

doi:10.1556/amicr.60.2013.2.6

Cited by 11 publications

(7 citation statements)

References 16 publications

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“…In this study, we found that most CGD patients have hypergammaglobulinemia. Similar results were also demonstrated by the previous studies . The positive detection rate of pathogens was low in our study, which was similar to that observed in a previous study .…”

Section: Discussionsupporting

confidence: 93%

“…Similar results were also demonstrated by the previous studies. [18][19][20] The positive detection rate of pathogens was low in our study, which was similar to that observed in a previous study. 8 This might be due to previous long-term antibiotic/antifungal prophylactic therapy.…”

Section: Discussionsupporting

confidence: 90%

“…All data were analyzed using SPSS ver. 19.0 (International Business Machines Corporation, Chicago, IL, USA). Continuous data were expressed as the mean ± standard deviation or range.…”

Section: Me Thodsmentioning

confidence: 99%

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Clinical and genetic characteristics of Chinese pediatric patients with chronic granulomatous disease

Gao

Yin

Tong

et al. 2019

Pediatric Allergy Immunology

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BackgroundChronic granulomatous disease (CGD) is a rare disease in China, and very little large‐scale studies have been conducted to date. We aimed to investigate the clinical and genetic features of CGD in Chinese pediatric patients.MethodsPediatric patients with CGD from Beijing Children's Hospital, Capital Medical University, China, were enrolled from January 2006 to December 2016.ResultsA total of 159 pediatric patients with CGD were enrolled. The median age of clinical onset was 1.4 months, and 73% (116/159) had clinical onset symptoms before the 1 year of age. The most common site of invasion was the lungs. The lymph nodes, liver, and skin were more frequently invaded in X‐linked (XL) CGD patients than in autosomal recessive (AR) CGD patients (P < 0.05). Approximately 64% (92/144) of the pediatric patients suffered from abnormal response to BCG vaccination. The most frequent pathogens were Aspergillus and Mycobacterium tuberculosis. Gene analysis indicated that 132 cases (89%, 132/147) harbored CYBB pathogenic variants, 7 (5%, 7/147) carried CYBA pathogenic variants, 4 (3%, 4/147) had NCF1 pathogenic variants, and 4 (3%, 4/147) had NCF2 pathogenic variants. The overall mortality rate in this study was 43%, particularly the patients were males, with CYBB mutant and did not receive HSCT treatment.ConclusionsChronic granulomatous disease is a rare disease affecting Chinese children; however, it is often diagnosed at a later age, and thus, the mortality rate is relatively high. The prevalence and the severity of disease in XL‐CGD are higher than AR‐CGD.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 90%

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Clinical and genetic characteristics of Chinese pediatric patients with chronic granulomatous disease

Gao

Yin

Tong

et al. 2019

Pediatric Allergy Immunology

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“…Hyper-IgE syndrome (Job syndrome) was excluded in these children because of the clinical course. Elevated IgE occurred in some reported cases of IMD30, none of which were due to loss-of-function mutations (Altare et al, 1998; Caragol et al, 2003; Carvalho et al, 2003; Moraes-Vasconcelos et al, 2005; Luangwedchakarn et al, 2009), and in one case of Chronic Granulomatous Disease, which is a type of MSMD characterized by mycobacterial granuloma formation (Patiroglu et al, 2013). In the later case, IgA deficiency was also reported and no mutations in the STAT3 and DOCK8 genes, characteristic in hiper-IgE syndrome, were found.…”

Section: Discussionmentioning

confidence: 99%

Microbial Disease Spectrum Linked to a Novel IL-12Rβ1 N-Terminal Signal Peptide Stop-Gain Homozygous Mutation with Paradoxical Receptor Cell-Surface Expression

et al. 2017

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Patients with Mendelian Susceptibility to Mycobacterial Diseases (MSMD) exhibit variable vulnerability to infections by mycobacteria and other intramacrophagic bacteria (e.g., Salmonella and Klebsiella) and fungi (e.g., Histoplasma, Candida, Paracoccidioides, Coccidioides, and Cryptococcus). The hallmark of MSMD is the inherited impaired production of interferon gamma (IFN-γ) or the lack of response to it. Mutations in the interleukin (IL)-12 receptor subunit beta 1 (IL12RB1) gene accounts for 38% of cases of MSMD. Most IL12RB1 pathogenic allele mutations, including ten known stop-gain variants, cause IL-12Rβ1 complete deficiency (immunodeficiency-30, IMD30) by knocking out receptor cell-surface expression. IL12RB1 loss-of-function genotypes impair both IL-12 and IL-23 responses. Here, we assess the health effects of a rare, novel IL12RB1 stop-gain homozygous genotype with paradoxical IL-12Rβ1 cell-surface expression. We appraise four MSMD children from three unrelated Brazilian kindreds by clinical consultation, medical records, and genetic and immunologic studies. The clinical spectrum narrowed down to Bacillus Calmette-Guerin (BCG) vaccine-related suppurative adenitis in all patients with one death, and recrudescence in two, histoplasmosis, and recurrence in one patient, extraintestinal salmonellosis in one child, and cutaneous vasculitis in another. In three patients, we established the homozygous Trp7Ter predicted loss-of-function inherited genotype and inferred it from the heterozygote parents of the fourth case. The Trp7Ter mutation maps to the predicted IL-12Rβ1 N-terminal signal peptide sequence. BCG- or phytohemagglutinin-blasts from the three patients have reduced cell-surface expression of IL-12Rβ1 with impaired production of IFN-γ and IL-17A. Screening of 227 unrelated healthy subjects from the same geographic region revealed one heterozygous genotype (allele frequency 0.0022) vs. one in over 841,883 public genome/exomes. We also show that the carriers bear European ancestry-informative alleles and share the extended CACCAGTCCGG IL12RB1 haplotype that occurs worldwide with a frequency of 8.4%. We conclude that the novel IL12RB1 N-terminal signal peptide stop-gain loss-of-function homozygous genotype confers IL-12Rβ1 deficiency with varying severity and early-onset age through diminished cell-surface expression of an impaired IL-12Rβ1 polypeptide. We firmly recommend attending to warning signs of IMD30 in children who are HIV-1 negative with a history of adverse effects to the BCG vaccine and presenting with recurrent Histoplasma spp. and extraintestinal Salmonella spp. infections.

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“…An exuberant respiratory inflammation induced by the exposure to inciting antigens and clinically manifested as hypersensitivity pneumonitis (HP) or allergic bronchopulmonary aspergillosis (ABPA) has also been described in CGD [ 2 – 7 ]. However, HP as an initial presentation of CGD is uncommon and has never been reported.…”

Section: Letter To the Editormentioning

confidence: 99%

Mimicking hypersensitivity pneumonitis as an uncommon initial presentation of chronic granulomatous disease in children

Liu

et al. 2017

Orphanet J Rare Dis

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Dry cough, dyspenea and diffuse centrilobular nodules in both lungs of radiologic findings similar to hypersensitivity pneumonitis (HP) are rare initial presentation in chronic granulomatous disease (CGD). CGD is remarkable for increased susceptibility to bacterial and fungal infections as well as high sensitivity to inciting antigens such as Aspergillus species due to dysregulated inflammation. We identified three children who had an initial presentation mimicking HP and were subsequently diagnosed as CGD. All patients developed invasive pulmonary A. fumigatus infection (IPAI) following systemic glucocorticoid therapy. Two of the three patients were found to have mutations in NCF1 gene and one patient in NCF2 gene. As HP is uncommon in children, we should consider the possibility of CGD in children with HP, even in mimicking HP patients with suggestive inhalation history and negative fungal cultures. A prompt diagnosis of CGD is essential to enable initiation of prophylactic antibacterial and antifungal therapies.

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Chronic granulomatous disease with markedly elevated IgE levels mimicking hyperimmunoglobulin E syndrome

Cited by 11 publications

References 16 publications

Clinical and genetic characteristics of Chinese pediatric patients with chronic granulomatous disease

Clinical and genetic characteristics of Chinese pediatric patients with chronic granulomatous disease

Microbial Disease Spectrum Linked to a Novel IL-12Rβ1 N-Terminal Signal Peptide Stop-Gain Homozygous Mutation with Paradoxical Receptor Cell-Surface Expression

Mimicking hypersensitivity pneumonitis as an uncommon initial presentation of chronic granulomatous disease in children

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