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J Allergy Clin Immunol. 2014 Aug;134(2):276-84. doi: 10.1016/j.jaci.2014.06.015.

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

Author information

1
Department of Pediatrics, Child & Family Research Institute, and BC Children's Hospital, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address: sturvey@cw.bc.ca.
2
National Institute of Health and Medical Research and the Department of Immunology and Hematology, Assistance Publique-Hopitaux de Paris, Necker Children's Hospital, Paris, and Descartes-Sorbonne Paris Cité University of Paris, Imagine Institute, Paris, France.
3
National Institute of Health and Medical Research and the Department of Immunology and Hematology, Assistance Publique-Hopitaux de Paris, Necker Children's Hospital, Paris, and Descartes-Sorbonne Paris Cité University of Paris, Imagine Institute, Paris, France; Unité d'immuno-hématologie pédiatrique, Hôpital Necker-Enfant Malades, Assistance Publique des Hôpitaux de Paris (APHP), Paris, France.
4
Department of Pediatrics, Child & Family Research Institute, and BC Children's Hospital, University of British Columbia, Vancouver, British Columbia, Canada.
5
Division of Immunology, Boston Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, Mass.
6
German Cancer Consortium (DKTK), partner site Munich at the Institut für Klinische Chemie und Pathobiochemie, Klinikum rechts der Isar, Technische Universität München, Munich, and German Cancer Research Center (DKFZ), Heidelberg, Germany.
7
Institute for Immunology, University of Heidelberg, Heidelberg, Germany.
8
Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Heidelberg, Germany.
9
Centre for Chronic Immunodeficiency (CCI), University Medical Center Freiburg and University of Freiburg, Freiburg, Germany.
10
Department of Medical Genetics, Child & Family Research Institute and BC Children's Hospital, University of British Columbia, Vancouver, British Columbia, Canada.
11
Unité d'immuno-hématologie pédiatrique, Hôpital Necker-Enfant Malades, Assistance Publique des Hôpitaux de Paris (APHP), Paris, France.
12
Institut für Klinische Chemie und Pathobiochemie, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
13
Department of Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, Md.
14
Pediatric Hematology-Oncology and Bone Marrow Transplantation, Hadassah Hebrew University Medical Center, Jerusalem, Israel.

Abstract

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 a unique opportunity to study the effect 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 caspase recruitment domain family, member 11 (CARD11)-B-cell chronic lymphocytic leukemia/lymphoma 10 (BCL10)-mucosa-associated lymphoid tissue lymphoma translocation gene 1 (MALT1 [CBM]) signalosome complex. The CBM complex forms an essential molecular link between the triggering of cell-surface antigen receptors and nuclear factor κB activation. Germline mutations affecting the CBM complex are now recognized as the cause of novel combined immunodeficiency phenotypes, which all share abnormal nuclear factor κB activation and dysregulated B-cell development as defining features. For this "Current perspectives" article, 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.

KEYWORDS:

CARD11-BCL10-MALT1 signalosome complex; CARMA1; combined immunodeficiency; congenital B-cell lymphocytosis; next-generation sequencing; nuclear factor κB; paracaspase; primary immunodeficiency diseases

PMID:
25087226
PMCID:
PMC4167767
DOI:
10.1016/j.jaci.2014.06.015
[Indexed for MEDLINE]
Free PMC Article

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