Mycobacterium Fortuitum-Chelonae Complex Infection in a Child With Complete Interleukin-12 Receptor Beta 1 Deficiency

Aksu, Güzide; Tirpan, Cengiz; Çavuşoğlu, Cengiz; Soydan, Saliha; Altare, Frédéric; Casanova, Jean‐Laurent; Kütükçüler, Necil

doi:10.1097/00006454-200105000-00021

Cited by 55 publications

(34 citation statements)

References 14 publications

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“…Recessive mutations in the gene encoding the IL12 receptor b1 chain (IL12Rb1) were found in these patients causing complete IL12Rb1 deficiency. [94][95][96][97][98][99] Most recently, recessive mutations in the IL12B gene have been described in 13 patients from India and Saudi Arabia. These mutations resulted in complete absence of the IL12 p40 subunit.…”

Section: Familial Atypical Mycobacteriosis and Abnormal Ifng Signallingmentioning

confidence: 99%

Susceptibility to mycobacterial infections: the importance of host genetics

2003

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There is substantial evidence that host genetic factors are important in determining susceptibility to mycobacteria. Several different techniques have been used to identify the genes involved. Studies of an inbred strain of mice with increased susceptibility to mycobacteria, salmonella and leishmania infections led to the identification of the natural resistance-associated macrophage protein gene (Nramp1). Case-control studies have confirmed the importance of the human equivalent of this gene, NRAMP1, and have also suggested that the major histocompatibility complex and vitamin-D receptor genes may be involved in determining human susceptibility to mycobacteria. Studies of individuals with the rare condition of increased susceptibility to disseminated bacille Calmette-Guerin and other atypical mycobacterial infections have identified several abnormalities in the genes encoding the interferon gamma receptor (IFNgR) ligand binding chain, IFNgR signal transduction chain, IFNg signal transduction and activation of transcription-1, interleukin 12 receptor b1 subunit and interleukin 12 p40 subunit. A genome-wide linkage study has been performed to identify genes exerting a major effect on tuberculosis susceptibility in the general population. Linkages were found to markers on chromosomes 15 and X. Studies to identify the genes responsible are in progress.

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Section: Familial Atypical Mycobacteriosis and Abnormal Ifng Signallingmentioning

confidence: 99%

Susceptibility to mycobacterial infections: the importance of host genetics

2003

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“…The 700 ϩ 362_1619-944 del IL12RB1 allele therefore encodes a detectable surface-expressed IL-12R␤1 chain in our patient. Remarkably, none of the other 53 patients with IL-12R␤1 deficiency described to date [17][18][19][20][21][22][23][24][25][26]28 were found to express detectable levels of these receptors at the cell surface. In contrast, IL-12R␤1 was present in large amounts at the cell surface in P and was detected with 5 of the 6 mAbs tested, including 2 of the 3 commercially available mAbs.…”

Section: A Detectable Il-12r␤1 Chain On the Cell Surfacementioning

confidence: 99%

“…5 Complete recessive STAT-1 deficiency is a related but distinct disorder involving susceptibility to both mycobacteria and viruses, due to the impairment of IFN-␥-and IFN-␣/␤-mediated immunity. 14 From [17][18][19][20][21][22][23][24][25][26]28 have no detectable IL-12R␤1 on the cell surface, due to mutations that either interrupt the open reading frame (ORF) (nonsense and frameshift mutations) or disrupt folding of the protein (missense mutations). We report here the molecular investigation of a patient with complete IL-12R␤1 deficiency despite the presence of IL-12R␤1 at the cell surface.…”

Section: Introductionmentioning

confidence: 99%

A novel form of complete IL-12/IL-23 receptor 1 deficiency with cell surface-expressed nonfunctional receptors

Fieschi¹

2004

Blood

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IntroductionMendelian susceptibility to mycobacterial disease (MSMD) (Mendelian Inheritance in Man, MIM209950; Online Mendelian Inheritance in Man [OMIM]: http://www.ncbi.nlm.nih.gov/ Omim/) 1 is a rare syndrome predisposing affected individuals to infectious diseases caused by poorly virulent mycobacteria, such as bacille Calmette-Guérin (BCG) vaccines and environmental mycobacteria (EM), and poorly virulent Salmonella strains, such as nontyphoidal "minor" serovars. Patients are also susceptible to infections caused by the more virulent Mycobacterium tuberculosis and typhoidal "major" Salmonella serotypes. 1,2 Unlike patients with "classic" immunodeficiencies, these patients are otherwise quite healthy and only rarely suffer from other unusually severe bacterial, viral, fungal, or parasitic diseases. 2,3 The spectrum of infections is narrow, but the spectrum of severity is broad-from disseminated BCG disease in infancy to localized environmental mycobacterial disease in the elderly. Moreover, whereas some sporadic and most familial cases seem to involve autosomal recessive heredity, the syndrome has been found to segregate in an autosomal dominant 4,5 or X-linked recessive 6 pattern in other families, further suggesting genetic heterogeneity.Five disease-causing autosomal genes have been identified since 1996, 7,8 and allelic heterogeneity accounts for the existence of 9 defined disorders, all of which result in impaired interferon-␥ (IFN-␥)-mediated immunity. 1,2 Null recessive mutations in the IFN-␥ receptor ligand-binding chain (IFN-␥R1)-encoding gene (IFNGR1) abolish either receptor expression 7,8 or the binding of surface-expressed receptors to IFN-␥. 9,10 Partial recessive 11 and dominant 4 IFN-␥R1 deficiencies have also been described. Different recessive mutations in the gene encoding the IFN-␥ signaling chain (IFN-␥R2), IFNGR2, are responsible for complete 12 or partial 13 IFN-␥R2 deficiency. A dominant mutation in STAT1 is responsible for partial signal transducer and activator of transcription-1 (STAT-1) deficiency and defines the remaining disease in which cellular responses to IFN-␥ are impaired. 5 Complete recessive STAT-1 deficiency is a related but distinct disorder involving susceptibility to both mycobacteria and viruses, due to the impairment of IFN-␥-and IFN-␣/␤-mediated immunity. 14 From [17][18][19][20][21][22][23][24][25][26]28 have no detectable IL-12R␤1 on the cell surface, due to mutations that either interrupt the open reading frame (ORF) (nonsense and frameshift mutations) or disrupt folding of the protein (missense mutations). We report here the molecular investigation of a patient with complete IL-12R␤1 deficiency despite the presence of IL-12R␤1 at the cell surface. Patients, materials, and methods The patientThe patient (P) is a 6-year-old boy born to first-cousin parents of Bedouin origin living in Israel (Figure 1). He was not inoculated with BCG and was first seen at the age of 12 months with disseminated Salmonella enteritidis disease (septicemia and multiple adenitis). Betw...

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“…Similarly, all but one of the cases of IL-12R␤1-deficient individuals have had complete deficiencies, which have been inherited in an autosomal recessive fashion (5,8,11,71,88,247,274). One leaky mutation in the IL-12R␤1 gene has been described, and the only manifestation in this patient was recurrent M. bovis BCG infections (212).…”

Section: Disorders Associated With Defective Production Of Gamma Intementioning

confidence: 99%

Infections in Patients with Inherited Defects in Phagocytic Function

2003

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Patients with defects in phagocytic function are predisposed to intracellular microorganisms and typically have early dissemination of the infection. Recognition of the underlying disorder and aggressive antimicrobial therapy has been beneficial for the patients. Improved understanding of the pathophysiology has also affected patient management by allowing specific, targeted immunomodulatory intervention. The disorders described in this review are not common but have had a significant impact on our understanding of the role of phagocytic cells in host defense. Conversely, understanding the role of the neutrophil and macrophage in infection has benefited not just the patients described in this review but also other patients with similar disease processes

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Mycobacterium Fortuitum-Chelonae Complex Infection in a Child With Complete Interleukin-12 Receptor Beta 1 Deficiency

Cited by 55 publications

References 14 publications

Susceptibility to mycobacterial infections: the importance of host genetics

Susceptibility to mycobacterial infections: the importance of host genetics

A novel form of complete IL-12/IL-23 receptor 1 deficiency with cell surface-expressed nonfunctional receptors

Infections in Patients with Inherited Defects in Phagocytic Function

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