RT Journal Article
T1 Inherited BCL10 deficiency impairs hematopoietic and nonhematopoietic immunity
A1 Torres, Juan Manuel
A1 Martínez Barricarte, Rubén
A1 García Gómez, Sonia
A1 Mazariegos, Marina S
A1 Itan, Yuval
A1 Boisson, Bertrand
A1 Álvarez Carbajal, Rita Lucía
A1 Jiménez Reinoso, Anaïs
A1 del Pino, Lucía
A1 Rodríguez Pena, Rebeca
A1 Ferreira Martín, Antonio
A1 Hernández Jiménez, Enrique
A1 Toledano, Víctor
A1 Cubillos Zapata, Carolina
A1 Díaz Almirón, Mariana
A1 López Collazo, Eduardo
A1 Unzueta Roch, José L
A1 Sánchez Ramón, Silvia María
A1 Regueiro González-Barros, José Ramón
A1 López Granados, Eduardo
A1 Casanova, Jean-Laurent
A1 Pérez de Diego, Rebeca
AB 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.
PB American Society for Clinical Investigation
SN 0021-9738 (print), 1558-8238 (online)
YR 2014
FD 2014-11
LK https://hdl.handle.net/20.500.14352/34396
UL https://hdl.handle.net/20.500.14352/34396
LA eng
NO Ministerio de Economia y Competitividad (MINECO)
NO Fundación Lair
DS Docta Complutense
RD 27 abr 2025