IKBKG (nuclear factor-κB essential modulator) mutation can be associated with opportunistic infection without impairing Toll-like receptor function

Salt, B.H.; Niemela, Julie E.; Pandey, Rahul; Hanson, Eric P.; Deering, Raquel P.; Quinones, Ralph; Jain, Ashish; Orange, Jordan S.; Gelfand, Erwin W.

doi:10.1016/j.jaci.2007.11.014

Cited by 44 publications

(41 citation statements)

References 32 publications

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“…Between 2002 and 2016, 13 patients with XL-EDA-ID were reported to have undergone HSCT (Dupuis-Girod et al 2002;Orange et al 2004;Tono et al 2007;Mancini et al 2008;Pai et al 2008;Salt et al 2008;Fish et al 2009;Minakawa et al 2009;Permaul et al 2009;Imamura et al 2011;Kawai et al 2012;Abbott et al 2014;Carlberg et al 2014;Klemann et al 2016). A summary of patient characteristics prior to HSCT can be found in Table 1.…”

Section: X-linked Ectodermal Dysplasia With Immunodeficiencymentioning

confidence: 99%

Hematopoietic stem cell transplantations for primary immune deficiencies associated with NFκB mutations: A review of the literature

Scott

Grunebaum

2017

LymphoSign Journal

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The nuclear factor kappa-light-chain-enhancer of activated B-cells (NFκB) family of transcription factors plays an instrumental role in human immunity and lymphoid organ development. Inherited defects affecting these factors or their regulation are associated with increased susceptibility to infections, as well as non-immune abnormalities. Hematopoietic stem cell transplantations (HSCT) have been shown to correct the immune abnormalities in a few patients with NFκB pathway defects. Here we review the pre-HSCT characteristics, as well as the HSCT and outcome of 35 patients who received HSCT for NFκB defects. Twenty-three patients (65.7%) were reported to have survived HSCT. Survival was higher among patients with X-linked ectodermal dysplasia and immunodeficiency (XL-EDA-ID), and those with CARD11-BCL10-MALT1 (CBM) complex defects, in comparison to patients with autosomal dominant ectodermal dysplasia and immunodeficiency (AD-EDA-ID) and IKBKB defects. Survival following myeloablative conditioning was similar to that after reduced intensity conditioning, although donor cells engraftment and immune reconstitution after HSCT was not complete in some patients. The effects of HSCT on organ dysfunction associated with NFκB defects, such as liver toxicity or bowel inflammation, are still not clear. Earlier identification and transplantation of affected patients, as well as better understanding of the pathogenesis and complications of the different NFκB mutations, might improve outcome of HSCT for specific patient populations. Statement of novelty:This review highlights the current indications, regimens, and outcome of HSCT for inherited defects involving various components of the canonical and non-canonical NFκB pathways.

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Section: X-linked Ectodermal Dysplasia With Immunodeficiencymentioning

confidence: 99%

Hematopoietic stem cell transplantations for primary immune deficiencies associated with NFκB mutations: A review of the literature

Scott

Grunebaum

2017

LymphoSign Journal

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“…With regard to fungal disease, patients with IKBA mutations are universally affected by CMC and 60% of them develop PCP (Picard et al 2011); decreased numbers of IL-17 þ T cells have been reported in these patients (Schimke et al 2013). Instead, CMC and PCP are far less common in NEMO-deficient patients (,10%) (Salt et al 2008;Picard et al 2011). Both EDA-ID syndromes belong in the heterogeneous group of disorders termed hyper-IgM syndromes (HIGM), characterized by elevated IgM despite hypo-g-globulinemia as a result of defects in immunoglobulin class switch recombination.…”

Section: Anhidrotic Ectodermal Dysplasia With Immunodeficiency (Eda-id)mentioning

confidence: 99%

Mendelian Genetics of Human Susceptibility to Fungal Infection

Lionakis

Netea

Holland

2014

Cold Spring Harbor Perspectives in Medicine

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Correspondence: lionakism@niaid.nih.gov A recent surge in newly described inborn errors of immune function-related genes that result in susceptibility to fungal disease has greatly enhanced our understanding of the cellular and molecular basis of antifungal immune responses. Characterization of single-gene defects that predispose to various combinations of superficial and deep-seated infections caused by yeasts, molds, and dimorphic fungi has unmasked the critical role of novel molecules and signaling pathways in mucosal and systemic antifungal host defense. These experiments of nature offer a unique opportunity for developing new knowledge in immunological research and form the foundation for devising immune-based therapeutic approaches for patients infected with fungal pathogens.

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“…Clinical and laboratory features were previously reviewed and were significant for the absence of the somatic problems of oligodontia, ectodermal dysplasia or chronic gastrointestinal (GI) disease. 5 Despite both impaired natural killer (NK) cell function and impaired T-cell receptor (TCR) signaling, Toll-like receptor (TLR) signaling appeared to be intact. 5 The patient received a myeloablative conditioning regimen consisting of BU, CY and equine antithymocyte globulin (ATG) followed by 10/10-matched, unrelated umbilical cord blood allo-HSCT.…”

mentioning

confidence: 99%

“…5 Despite both impaired natural killer (NK) cell function and impaired T-cell receptor (TCR) signaling, Toll-like receptor (TLR) signaling appeared to be intact. 5 The patient received a myeloablative conditioning regimen consisting of BU, CY and equine antithymocyte globulin (ATG) followed by 10/10-matched, unrelated umbilical cord blood allo-HSCT. Post transplant, the patient developed allergies to sulfa and walnuts but did not develop chronic GI symptoms.…”

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confidence: 99%

Successful hematopoietic cell transplantation in patients with unique NF-κB essential modulator (NEMO) mutations

Abbott

Quinones

Morena

et al. 2014

Bone Marrow Transplant

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IKBKG (nuclear factor-κB essential modulator) mutation can be associated with opportunistic infection without impairing Toll-like receptor function

Abstract: Background-Patients with hypomorphic nuclear factor-κB essential modulator (NEMO) mutations have extensive phenotypic variability that can include atypical infectious susceptibility.

Cited by 44 publications

References 32 publications

Hematopoietic stem cell transplantations for primary immune deficiencies associated with NFκB mutations: A review of the literature

Hematopoietic stem cell transplantations for primary immune deficiencies associated with NFκB mutations: A review of the literature

Mendelian Genetics of Human Susceptibility to Fungal Infection

Successful hematopoietic cell transplantation in patients with unique NF-κB essential modulator (NEMO) mutations

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