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

Abbott, Jordan K.; Quinones, Ralph; Morena, M. Teresa de la; Gelfand, Erwin W.

doi:10.1038/bmt.2014.157

Cited by 15 publications

(12 citation statements)

References 11 publications

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“…This hypothesis is supported by the observation that in-vitro inhibition of NF-kappaB activity renders cells more susceptible to chemotherapy-induced apoptosis [25,26]. Currently, there is not sufficient data to indicate, whether reduced intensity conditioning (RIC) leads to better outcomes (supplementary table 1) [11,13,14,22–27]. In our patient, HSCT resulted in full donor chimerism and functional immune reconstitution (Fig.…”

Section: Case Reports Results and Discussionsupporting

confidence: 68%

Transplantation from a symptomatic carrier sister restores host defenses but does not prevent colitis in NEMO deficiency

Klemann

Pannicke

Morris-Rosendahl

et al. 2016

Clinical Immunology

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NF-κB essential modulator (NEMO) deficiency causes ectodermal dysplasia with immunodeficiency in males, while manifesting as incontinentia pigmenti in heterozygous females. We report a family with NEMO deficiency, in which a female carrier displayed skewed X-inactivation favoring the mutant NEMO allele associated with symptoms of Behçet's disease. Hematopoietic stem cell transplantation of an affected boy from this donor reconstituted an immune system with retained skewed X-inactivation. After transplantation no more severe infections occurred, indicating that an active wild-type NEMO allele in only 10% of immune cells restores host defense. Yet he developed inflammatory bowel disease (IBD). While gut infiltrating immune cells stained strongly for nuclear p65 indicating restored NEMO function, this was not the case in intestinal epithelial cells - in contrast to cells from conventional IBD patients. These results extend murine observations that epithelial NEMO-deficiency suffices to cause IBD. High anti-TNF doses controlled the intestinal inflammation and symptoms of Behçet's disease.

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Section: Case Reports Results and Discussionsupporting

confidence: 68%

Transplantation from a symptomatic carrier sister restores host defenses but does not prevent colitis in NEMO deficiency

Klemann

Pannicke

Morris-Rosendahl

et al. 2016

Clinical Immunology

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“…Regardless of the cause, the GI complications might have further contributed to the chronic diarrhea, feeding intolerance and (or) poor growth reported in 5 patients following HSCT. Immune evaluations done 2 years or more after HSCT demonstrated that those who received MAC from healthy donors had complete T and B cell reconstitution, with adequate response to conjugate and live virus vaccines (Abbott et al 2014). Altogether, the patients described above indicate that HSCT can correct the immune deficiency associated with NEMO deficiency, particularly if MAC is used and full donor chimerism is achieved.…”

Section: X-linked Ectodermal Dysplasia With Immunodeficiencymentioning

confidence: 90%

“…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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“…But this method of treatment also has problems and is not always successful. In patients who show bowel inflammation before the transplant, a transplant may worsen the condition [47,[49][50][51].…”

Section: Eda-id Treatmentmentioning

confidence: 99%

A Review of NEMO Protein and its Relationship with Genetic Diseases

Zinatizadeh¹,

Masoumalinejad²,

Nejatizadeh³

et al. 2018

J Genet Genome Res

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NF-κB essential modulator (NEMO) syndrome is an immunodeficiency disease. NF-κB proteins, which regulate the expression of genes that moderate important physiological processes, are called regulatory of cell homeostasis. NEMO is a protein in the IKK inhibitor complex that many organ systems normally do not grow. Cells (as well as organ and tissues) do not grow proteins they express proteins. The disease occurs due to mutation in the IKBKG gene. The IKBKG gene, located in the Xq28 chromosomal region or located in the X chromosome. The disease indicates an impairment of NF-κB activation and the initial treatment of NEMO is very difficult. About 70-80% of patients have similar DNA rearrangements. Epilepsy is observed in about 50% of patients with these disorders. Therefore, there is little information about the NEMO disease and more research is needed to further examine the syndrome.

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

Cited by 15 publications

References 11 publications

Transplantation from a symptomatic carrier sister restores host defenses but does not prevent colitis in NEMO deficiency

Transplantation from a symptomatic carrier sister restores host defenses but does not prevent colitis in NEMO deficiency

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

A Review of NEMO Protein and its Relationship with Genetic Diseases

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