Clinical features of dominant and recessive interferon γ receptor 1 deficiencies

Dorman, Susan E.; Pïcard, Capucine; Lammas, David A.; Heyne, K; Dissel, Jaap T. van; Baretto, Richard; Rosenzweig, Sergio D.; Newport, Melanie J.; Levin, Michael; Roesler, Joachim; Kumararatne, Dinakantha; Casanova, Jean Laurent; Holland, Steven M.

doi:10.1016/s0140-6736(04)17552-1

Cited by 392 publications

(393 citation statements)

References 36 publications

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“…As expected, the expression levels of all tested proteins were significantly elevated after MTB infection (Wilcoxon signed-rank test, FDR < 0.01, Fig. S2), and we observed strong induction of all of the cytokines presently known to play a critical 10 transformed P values test the null hypothesis of no difference in expression levels between untreated and infected DCs (y axis) and are plotted against the average log 2 fold changes in expression (x axis). Data for genes that were not classified as differentially expressed are plotted in black.…”

Section: Resultssupporting

confidence: 77%

“…The strongest evidence for this probably comes from twin studies showing that the rate of TB in monozygotic twins is more than twice that observed among dizygotic twins (8). In addition, studies on Mendelian susceptibility to mycobacterial disease (MSMD) have identified multiple rare single-gene mutations linked with susceptibility to mycobacteria (7,9,10). Although studies on MSMD have played a key role in identifying important pathways involved in protective immunity against TB, such as the IL12/23-and IFN-γ pathways (7,(9)(10)(11)(12)(13)(14), the mutations identified are too rare to have a significant impact on the overall variation in susceptibility to TB in the wider population.…”

mentioning

confidence: 99%

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Deciphering the genetic architecture of variation in the immune response toMycobacterium tuberculosisinfection

Barreiro

Tailleux²,

Pai³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

243

263

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Tuberculosis (TB) is a major public health problem. One-third of the world's population is estimated to be infected with Mycobacterium tuberculosis (MTB), the etiological agent causing TB, and active disease kills nearly 2 million individuals worldwide every year. Several lines of evidence indicate that interindividual variation in susceptibility to TB has a heritable component, yet we still know little about the underlying genetic architecture. To address this, we performed a genome-wide mapping study of loci that are associated with functional variation in immune response to MTB. Specifically, we characterized transcript and protein expression levels and mapped expression quantitative trait loci (eQTL) in primary dendritic cells (DCs) from 65 individuals, before and after infection with MTB. We found 198 response eQTL, namely loci that were associated with variation in gene expression levels in either untreated or MTB-infected DCs, but not both. These response eQTL are associated with natural regulatory variation that likely affects (directly or indirectly) host interaction with MTB. Indeed, when we integrated our data with results from a genome-wide association study (GWAS) for pulmonary TB, we found that the response eQTL were more likely to be genetically associated with the disease. We thus identified a number of candidate loci, including the MAPK phosphatase DUSP14 in particular, that are promising susceptibility genes to pulmonary TB.

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Section: Resultssupporting

confidence: 77%

mentioning

confidence: 99%

Deciphering the genetic architecture of variation in the immune response toMycobacterium tuberculosisinfection

Barreiro

Tailleux²,

Pai³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

243

263

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“…3 Consistently with our observation, patients with recessive complete IFNgR1 deficiency are younger, are infected with less pathogenic fast-growing mycobacteria and have more severe and disseminated infections than those with dominant partial deficiency. Several patients with dominant partial IFNgR1 deficiency have been reported with mycobacterial osteomyelitis initially misdiagnosed as Langerhans cell histio-cytosis (LCH).…”

supporting

confidence: 91%

“…6 One-third of them die from their first recognized mycobacterial infection while others have chronic disease that does not resolve on treatment or relapsed rapidly after discontinuation of antibiotics. 3 In addition to our patient, 11 HSCTs in 8 patients with complete IFNgR1 deficiency have been reported. 6 Four patients died shortly after HSCT, two survivors had very low engraftment and only two patients were in full remission of mycobacterial disease 5 years after HSCT from HLA-identical sibling.…”

supporting

confidence: 57%

“…1,2 Mutations leading to complete IFN-g receptor 1 (IFNgR1) deficiency have been identified in 22 patients from 17 kindreds and result in the most severe phenotype. 3 Hematopoietic stem cell transplantation (HSCT) has been proposed as the only curative treatment for patients with complete IFNgR1 deficiency. 4,5 The use of a non T-cell depleted transplant from an HLA-identical sibling and fully myeloablative conditioning regimen provide better results.…”

mentioning

confidence: 99%

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Successful hematopoietic stem cell transplantation in a child with active disseminated Mycobacterium fortuitum infection and interferon-γ receptor 1 deficiency

Chantrain

Bruwier

Brichard

et al. 2006

Bone Marrow Transplant

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Primary Immunodeficiency Affecting the Innate Immune System

Rosenzweig

2011

Encyclopedia of Life Sciences

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Primary immunodeficiencies are a heterogeneous group of genetically inherited diseases quantitively or functionally affecting innate or adaptive immunity. The innate and adaptive arms of the immune system work synergistically to efficiently control and neutralise the wide range of pathogens that challenge vertebrates. Although at first glance innate immunity might appear primitive, innate immune cells can orchestrate discrete immune responses to different infections through the recognition of diverse pathogens by germline‐encoded pattern recognition receptors. Neutrophils, macrophages, dendritic cells, natural killer (NK) cells and NKT cells, in conjunction with natural antimicrobial agents, opsonins (as Complement) and cytokines, are critical innate components in neutralising infectious agents. Primary immunodeficiencies are understood as a state of primary lack of protective immunity. Different compartments of the innate immune system are analysed in this article to highlight their critical pathophysiological role in host defences and protective immunity. Key Concepts: The innate immune system includes epithelial and mucosal barriers, cells, natural antimicrobial product, pattern recognition receptors (PRR) and cytokines to protect the host from infections without the need of previous exposure to those microorganisms. Neutrophil disorder should be suspected in patients with recurrent, severe, bacterial or fungal infections, especially those caused by unusual organisms. The mononuclear phagocytes are crucial for antigen presentation and for protection against intracellular infections, especially mycobacteria. Natural killer cell deficiency could involve quantitative and functional defects, in both cases showing increased susceptibility to viral infections. Natural killer T (NKT) cells constitute a distinctive subpopulation of mature lymphocytes that coexpress NK (CD56) and T (CD3) cell antigens and play a central role in infectious (e.g. virus), allergic (e.g. asthma) and autoimmune diseases (e.g. hepatitis), as well as tumour control. The complement system is a cascade system of more than 30 serum and membrane‐bound proteins that, when deficient, leads to impaired host defence and inappropriate inflammation.

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Clinical features of dominant and recessive interferon γ receptor 1 deficiencies

Cited by 392 publications

References 36 publications

Deciphering the genetic architecture of variation in the immune response toMycobacterium tuberculosisinfection

Deciphering the genetic architecture of variation in the immune response toMycobacterium tuberculosisinfection

Successful hematopoietic stem cell transplantation in a child with active disseminated Mycobacterium fortuitum infection and interferon-γ receptor 1 deficiency

Primary Immunodeficiency Affecting the Innate Immune System

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