Human BCL10 Deficiency due to Homozygosity for a Rare Allele

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dc.contributor.authorVan Den Rym, Ana
dc.contributor.authorPerez de Diego, Rebeca
dc.contributor.authorSánchez Ramón, Silvia María
dc.contributor.authorAmin Safa
dc.date.accessioned2024-01-11T15:06:39Z
dc.date.available2024-01-11T15:06:39Z
dc.date.issued2020-02-01
dc.description.abstractThe 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 TFH 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.
dc.description.departmentDepto. de Inmunología, Oftalmología y ORL
dc.description.facultyFac. de Medicina
dc.description.refereedTRUE
dc.description.sponsorshipFIS (Fondo de Investigación Sanitaria)
dc.description.sponsorshipCAM (Comunidad Autónoma de Madrid)
dc.description.sponsorshipFundación Ramón Areces
dc.description.sponsorshipMINECO (Ministerio de Economía y competitividad)
dc.description.statuspub
dc.identifier.citationVan Den Rym A, Taur P, Martinez-Barricarte R, Lorenzo L, Puel A, Gonzalez-Navarro P, Pandrowala A, Gowri V, Safa A, Toledano V, Cubillos-Zapata C, López-Collazo E, Vela M, Pérez-Martínez A, Sánchez-Ramón S, Recio MJ, Casanova JL, Desai MM, Perez de Diego R. J Clin Immunol. 2020 Feb;40(2):388-398
dc.identifier.doi10.1007/s10875-020-00760-3
dc.identifier.issn0271-9142
dc.identifier.issn1573-2592
dc.identifier.officialurlhttps://link.springer.com/journal/10875
dc.identifier.urihttps://hdl.handle.net/20.500.14352/92584
dc.issue.number2
dc.journal.titleJournal of Clinical Immunology
dc.language.isoeng
dc.page.final398
dc.page.initial388
dc.publisherSpringer
dc.relation.projectIDPI14/00616
dc.relation.projectIDPI17/00543
dc.relation.projectIDSAF2014-54708-R
dc.relation.projectIDB2017/BMD3673
dc.rightsAttribution 4.0 Internationalen
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subject.keywordBCL10
dc.subject.keywordCBM complex
dc.subject.keywordAutosomal recessive
dc.subject.keywordCombined immunodeficiency
dc.subject.keywordComputational immunology
dc.subject.keywordMass cytometry
dc.subject.keywordNext-generation sequencing; primary immunodeficiency
dc.subject.ucmInmunología
dc.subject.unesco2412 Inmunología
dc.titleHuman BCL10 Deficiency due to Homozygosity for a Rare Allele
dc.typejournal article
dc.type.hasVersionVoR
dc.volume.number40
dspace.entity.typePublication
relation.isAuthorOfPublicationbea59590-c16b-4e29-b8d6-d7b2133b4533
relation.isAuthorOfPublication.latestForDiscoverybea59590-c16b-4e29-b8d6-d7b2133b4533
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