Functional T Cell Immunodeficiencies (with T Cells Present)

Notarangelo, Luigi D.

doi:10.1146/annurev-immunol-032712-095927

Cited by 50 publications

(43 citation statements)

References 191 publications

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“…Recently, beside hypomorphic variants of classic SCID-associated genes (e.g. variants of recombination-activating genes 1 & 2), mutations in an increasing number of new genes have been identified leading to a delayed onset of CID often associated with disturbed T cell homeostasis and function, rather than the absence of T cells 1, 51 . These patients often have a more variable clinical phenotype and have been a challenging group in terms of both diagnosis and therapeutic approach 49 .…”

Section: Cbm Complex Mutations As a Novel Cause Of Human Combined Immmentioning

confidence: 99%

The CARD11-BCL10-MALT1 (CBM) signalosome complex: Stepping into the limelight of human primary immunodeficiency

Turvey

Durandy²,

Fischer

et al. 2014

Journal of Allergy and Clinical Immunology

119

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Next-generation DNA sequencing has accelerated the genetic characterization of many human primary immunodeficiency diseases (PIDs). These discoveries can be lifesaving for the affected patients, and also provide the unique opportunity to study the impact of specific genes on human immune function. In the past 18 months, a number of independent groups have begun to define novel PIDs caused by defects in the CARD11–BCL10–MALT1 (CBM) signalasome complex. The CBM complex forms an essential molecular link between the triggering of cell surface antigen receptors and NF-κB activation. Germline mutations affecting the CBM complex are now recognized as the cause of novel combined immunodeficiency phenotypes which all share abnormal NF-κB activation and dysregulated B cell development as defining features. For this Current Perspectives we have engaged experts in both basic biology and clinical immunology to capture the worldwide experience in recognizing and managing patients with PIDs caused by CBM complex mutations.

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Section: Cbm Complex Mutations As a Novel Cause Of Human Combined Immmentioning

confidence: 99%

The CARD11-BCL10-MALT1 (CBM) signalosome complex: Stepping into the limelight of human primary immunodeficiency

Turvey

Durandy²,

Fischer

et al. 2014

Journal of Allergy and Clinical Immunology

119

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“…Up to 40 mutations in different genes have been found to cause these conditions (1)(2)(3), and 2 subgroups of CID have been defined: severe combined immunodeficiency (SCID) (4) and CID, which is generally less profound than SCID (5). SCID is characterized by a lack of autologous T cells, whereas CID patients have T cells.…”

Section: Introductionmentioning

confidence: 99%

Inherited BCL10 deficiency impairs hematopoietic and nonhematopoietic immunity

Torres¹,

Martı́nez-Barricarte²,

García-Gómez³

et al. 2014

J. Clin. Invest.

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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.

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“…While typical severe combined immunodeficiency (SCID) in humans is defined by a profound block in T lymphocyte production, with or without associated B and NK lymphocyte defects, more heterogeneous combined immunodeficiency (CID) disorders arise from gene defects that allow T lymphocytes to mature, but hinder their survival, release from the thymus into the periphery, or effector functions [2]. Individuals with CID may have both impairment of immune responses and defects in immune regulation; thus they may experience severe, recurrent and opportunistic infections as well as autoimmune disorders [3, 4]. …”

Section: Introductionmentioning

confidence: 99%