The CBM-opathies—A Rapidly Expanding Spectrum of Human Inborn Errors of Immunity Caused by Mutations in the CARD11-BCL10-MALT1 Complex
The caspase recruitment domain family member 11 (CARD11 or CARMA1)—B cell CLL/lymphoma 10 (BCL10)—MALT1 paracaspase (MALT1) [CBM] signalosome complex serves as a molecular bridge between cell surface antigen receptor signaling and the activation of the NF-κB, JNK, and mTORC1 signaling axes. This pos...
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Frontiers Media S.A.
2018-09-01
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author | Henry Y. Lu Henry Y. Lu Bradly M. Bauman Swadhinya Arjunaraja Batsukh Dorjbal Joshua D. Milner Andrew L. Snow Stuart E. Turvey Stuart E. Turvey |
author_facet | Henry Y. Lu Henry Y. Lu Bradly M. Bauman Swadhinya Arjunaraja Batsukh Dorjbal Joshua D. Milner Andrew L. Snow Stuart E. Turvey Stuart E. Turvey |
author_sort | Henry Y. Lu |
collection | DOAJ |
description | The caspase recruitment domain family member 11 (CARD11 or CARMA1)—B cell CLL/lymphoma 10 (BCL10)—MALT1 paracaspase (MALT1) [CBM] signalosome complex serves as a molecular bridge between cell surface antigen receptor signaling and the activation of the NF-κB, JNK, and mTORC1 signaling axes. This positions the CBM complex as a critical regulator of lymphocyte activation, proliferation, survival, and metabolism. Inborn errors in each of the CBM components have now been linked to a diverse group of human primary immunodeficiency diseases termed “CBM-opathies.” Clinical manifestations range from severe combined immunodeficiency to selective B cell lymphocytosis, atopic disease, and specific humoral defects. This surprisingly broad spectrum of phenotypes underscores the importance of “tuning” CBM signaling to preserve immune homeostasis. Here, we review the distinct clinical and immunological phenotypes associated with human CBM complex mutations and introduce new avenues for targeted therapeutic intervention. |
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publishDate | 2018-09-01 |
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spelling | doaj.art-fc9b217475794043b60da4cb16a62ade2022-12-22T03:49:50ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-09-01910.3389/fimmu.2018.02078415218The CBM-opathies—A Rapidly Expanding Spectrum of Human Inborn Errors of Immunity Caused by Mutations in the CARD11-BCL10-MALT1 ComplexHenry Y. Lu0Henry Y. Lu1Bradly M. Bauman2Swadhinya Arjunaraja3Batsukh Dorjbal4Joshua D. Milner5Andrew L. Snow6Stuart E. Turvey7Stuart E. Turvey8Department of Pediatrics, British Columbia Children's Hospital, The University of British Columbia, Vancouver, BC, CanadaExperimental Medicine Program, Faculty of Medicine, The University of British Columbia, Vancouver, BC, CanadaDepartment of Pharmacology and Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, MD, United StatesDepartment of Pharmacology and Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, MD, United StatesDepartment of Pharmacology and Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, MD, United StatesLaboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United StatesDepartment of Pharmacology and Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, MD, United StatesDepartment of Pediatrics, British Columbia Children's Hospital, The University of British Columbia, Vancouver, BC, CanadaExperimental Medicine Program, Faculty of Medicine, The University of British Columbia, Vancouver, BC, CanadaThe caspase recruitment domain family member 11 (CARD11 or CARMA1)—B cell CLL/lymphoma 10 (BCL10)—MALT1 paracaspase (MALT1) [CBM] signalosome complex serves as a molecular bridge between cell surface antigen receptor signaling and the activation of the NF-κB, JNK, and mTORC1 signaling axes. This positions the CBM complex as a critical regulator of lymphocyte activation, proliferation, survival, and metabolism. Inborn errors in each of the CBM components have now been linked to a diverse group of human primary immunodeficiency diseases termed “CBM-opathies.” Clinical manifestations range from severe combined immunodeficiency to selective B cell lymphocytosis, atopic disease, and specific humoral defects. This surprisingly broad spectrum of phenotypes underscores the importance of “tuning” CBM signaling to preserve immune homeostasis. Here, we review the distinct clinical and immunological phenotypes associated with human CBM complex mutations and introduce new avenues for targeted therapeutic intervention.https://www.frontiersin.org/article/10.3389/fimmu.2018.02078/fullCBM complexCARD11MALT1BCL10combined immunodeficiencysevere combined immunodeficiency |
spellingShingle | Henry Y. Lu Henry Y. Lu Bradly M. Bauman Swadhinya Arjunaraja Batsukh Dorjbal Joshua D. Milner Andrew L. Snow Stuart E. Turvey Stuart E. Turvey The CBM-opathies—A Rapidly Expanding Spectrum of Human Inborn Errors of Immunity Caused by Mutations in the CARD11-BCL10-MALT1 Complex Frontiers in Immunology CBM complex CARD11 MALT1 BCL10 combined immunodeficiency severe combined immunodeficiency |
title | The CBM-opathies—A Rapidly Expanding Spectrum of Human Inborn Errors of Immunity Caused by Mutations in the CARD11-BCL10-MALT1 Complex |
title_full | The CBM-opathies—A Rapidly Expanding Spectrum of Human Inborn Errors of Immunity Caused by Mutations in the CARD11-BCL10-MALT1 Complex |
title_fullStr | The CBM-opathies—A Rapidly Expanding Spectrum of Human Inborn Errors of Immunity Caused by Mutations in the CARD11-BCL10-MALT1 Complex |
title_full_unstemmed | The CBM-opathies—A Rapidly Expanding Spectrum of Human Inborn Errors of Immunity Caused by Mutations in the CARD11-BCL10-MALT1 Complex |
title_short | The CBM-opathies—A Rapidly Expanding Spectrum of Human Inborn Errors of Immunity Caused by Mutations in the CARD11-BCL10-MALT1 Complex |
title_sort | cbm opathies a rapidly expanding spectrum of human inborn errors of immunity caused by mutations in the card11 bcl10 malt1 complex |
topic | CBM complex CARD11 MALT1 BCL10 combined immunodeficiency severe combined immunodeficiency |
url | https://www.frontiersin.org/article/10.3389/fimmu.2018.02078/full |
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