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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Published inFrontiers in immunology Vol. 9; p. 2078
Main Authors Lu, Henry Y., Bauman, Bradly M., Arjunaraja, Swadhinya, Dorjbal, Batsukh, Milner, Joshua D., Snow, Andrew L., Turvey, Stuart E.
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Media S.A 19.09.2018
Subjects
BCL10
CARD11
CBM complex
combined immunodeficiency
Immunology
MALT1
severe combined immunodeficiency
CBM complex
primary atopic disease
BENTA
BCL10
severe combined immunodeficiency
CARD11
MALT1
combined immunodeficiency
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Summary: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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This article was submitted to Primary Immunodeficiencies, a section of the journal Frontiers in Immunology
These authors have contributed equally to this work
Reviewed by: Ruben Martinez-Barricarte, Rockefeller University, United States; Jolan Eszter Walter, University of South Florida, United States
Edited by: Elissa Deenick, Garvan Institute of Medical Research, Australia
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2018.02078