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Clinical and Immunological Features of Human BCL10 Deficiency.
- Source :
-
Frontiers in immunology [Front Immunol] 2021 Nov 12; Vol. 12, pp. 786572. Date of Electronic Publication: 2021 Nov 12 (Print Publication: 2021). - Publication Year :
- 2021
-
Abstract
- The CARD-BCL10-MALT1 (CBM) complex is critical for the proper assembly of human immune responses. The clinical and immunological consequences of deficiencies in some of its components such as CARD9, CARD11, and MALT1 have been elucidated in detail. However, the scarcity of BCL10 deficient patients has prevented gaining detailed knowledge about this genetic disease. Only two patients with BCL10 deficiency have been reported to date. Here we provide an in-depth description of an additional patient with autosomal recessive complete BCL10 deficiency caused by a nonsense mutation that leads to a loss of expression (K63X). Using mass cytometry coupled with unsupervised clustering and machine learning computational methods, we obtained a thorough characterization of the consequences of BCL10 deficiency in different populations of leukocytes. We showed that in addition to the near absence of memory B and T cells previously reported, this patient displays a reduction in NK, γδT, Tregs, and T <subscript>FH</subscript> cells. The patient had recurrent respiratory infections since early childhood, and showed a family history of lethal severe infectious diseases. Fortunately, hematopoietic stem-cell transplantation (HSCT) cured her. Overall, this report highlights the importance of early genetic diagnosis for the management of BCL10 deficient patients and HSCT as the recommended treatment to cure this disease.<br />Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.<br /> (Copyright © 2021 Garcia-Solis, Van Den Rym, Pérez-Caraballo, Al–Ayoubi, Alazami, Lorenzo, Cubillos-Zapata, López-Collazo, Pérez-Martínez, Allende, Markle, Fernández-Arquero, Sánchez-Ramón, Recio, Casanova, Mohammed, Martinez-Barricarte and Pérez de Diego.)
- Subjects :
- B-Cell CLL-Lymphoma 10 Protein genetics
Child
Codon, Nonsense
DNA Mutational Analysis
Female
Hematopoietic Stem Cell Transplantation
Humans
Lymphocytes metabolism
Primary Immunodeficiency Diseases genetics
Primary Immunodeficiency Diseases immunology
Primary Immunodeficiency Diseases therapy
B-Cell CLL-Lymphoma 10 Protein deficiency
Lymphocytes immunology
Primary Immunodeficiency Diseases diagnosis
Subjects
Details
- Language :
- English
- ISSN :
- 1664-3224
- Volume :
- 12
- Database :
- MEDLINE
- Journal :
- Frontiers in immunology
- Publication Type :
- Academic Journal
- Accession number :
- 34868072
- Full Text :
- https://doi.org/10.3389/fimmu.2021.786572