Whole-exome sequencing links caspase recruitment domain 11 (CARD11) inactivation to severe combined immunodeficiency

Greil, Johann; Rausch, Tobias; Giese, Thomas; Bandapalli, Obul Reddy; Daniel, Volker; Bekeredjian‐Ding, Isabelle; Stütz, Adrian M.; Drees, Christoph; Roth, Susanne; Ruland, Jürgen; Korbel, Jan; Kulozik, Andreas E.

doi:10.1016/j.jaci.2013.02.012

Cited by 127 publications

(99 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The CBM complex is involved in NF-κB activation after stimulation of various receptors on lymphoid, myeloid, and epithelial cells (11)(12)(13). Deficiencies in MALT1 and CARD11 (also known as CARMA1) are associated with CID and SCID, respectively, and CARD9 deficiency has been shown to compromise innate immunity to a small number of fungi in a selective manner (6)(7)(8)(9)(10). Here, our investigations of a child with CID revealed inherited BCL10 deficiency.…”

Section: Introductionmentioning

confidence: 69%

“…The absence of regulatory T cells may have contributed to the inflammatory chronic colitis observed in P1. Mutations of human genes encoding partner proteins of BCL10, such as MALT1 (6), CARD11 (8,10), and CARD9 (7,9), have also recently been described. Interestingly, the clinical and immunological phenotypes of patients with these mutations differ from those of P1 with BCL10 deficiency.…”

Section: Discussionmentioning

confidence: 99%

“…Unfortunately, it is not always easy to distinguish between these conditions, and it can therefore be difficult to assess prognosis. Inborn defects of the CBM complex -consisting of caspase recruitment domain-containing (CARD) family adaptors, B cell CLL/lymphoma 10 (BCL10), and mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) -have recently been shown to underlie SCID, CID, and other immunological phenotypes (6)(7)(8)(9)(10). The CBM complex is involved in NF-κB activation after stimulation of various receptors on lymphoid, myeloid, and epithelial cells (11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Inherited BCL10 deficiency impairs hematopoietic and nonhematopoietic immunity

Torres¹,

Martı́nez-Barricarte²,

García-Gómez³

et al. 2014

J. Clin. Invest.

View full text Add to dashboard Cite

Heterotrimers composed of B cell CLL/lymphoma 10 (BCL10), mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1), and caspase recruitment domain-containing (CARD) family adaptors play a role in NF-κB activation and have been shown to be involved in both the innate and the adaptive arms of immunity in murine models. Moreover, individuals with inherited defects of MALT1, CARD9, and CARD11 present with immunological and clinical phenotypes. Here, we characterized a case of autosomal-recessive, complete BCL10 deficiency in a child with a broad immunodeficiency, including defects of both hematopoietic and nonhematopoietic immunity. The patient died at 3 years of age and was homozygous for a loss-of-expression, loss-of-function BCL10 mutation. The effect of BCL10 deficiency was dependent on the signaling pathway, and, for some pathways, the cell type affected. Despite the noted similarities to BCL10 deficiency in mice, including a deficient adaptive immune response, human BCL10 deficiency in this patient resulted in a number of specific features within cell populations. Treatment of the patient's myeloid cells with a variety of pathogen-associated molecular pattern molecules (PAMPs) elicited a normal response; however, NF-κB-mediated fibroblast functions were dramatically impaired. The results of this study indicate that inherited BCL10 deficiency should be considered in patients with combined immunodeficiency with B cell, T cell, and fibroblast defects.

show abstract

Section: Introductionmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Inherited BCL10 deficiency impairs hematopoietic and nonhematopoietic immunity

Torres¹,

Martı́nez-Barricarte²,

García-Gómez³

et al. 2014

J. Clin. Invest.

View full text Add to dashboard Cite

show abstract

“…Although mutations in all 3 CBM signalosome proteins have been described, HSCT has only been reported between 2013 and 2016 in 6 patients with MALT1 and CARD11 mutations (Greil et al 2013;Stepensky et al 2013;Punwani et al 2015;Charbit-Henrion et al 2016;Rozmus et al 2016). A summary of patient characteristics can be found in Table 7.…”

Section: Card11-bcl10-malt1 Complex 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

View full text Add to dashboard Cite

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.

show abstract

“…12 Human immune deficiencies arising from null mutations of CARD11 and MALT1 indicate that the canonical pathway is crucial for B-and T-cell activation, but these defects alone do not affect numbers of cells in the periphery. 13,14 BAFFR ligation activates the noncanonical NF-kB pathway, and deletion of Nfkb2 in mouse models results in disorganization of secondary lymphoid architecture and defective germinal center B-cell formation and differentiation. 15 By contrast, deletion of BAFFR itself in mice (Tnfrsf13c The online version of this article contains a data supplement.…”

Section: Introductionmentioning

confidence: 99%