Format

Send to

Choose Destination
J Clin Immunol. 2020 Jan 2. doi: 10.1007/s10875-019-00729-x. [Epub ahead of print]

A Novel, Heterozygous Three Base-Pair Deletion in CARD11 Results in B Cell Expansion with NF-κB and T Cell Anergy Disease.

Author information

1
Clinical Immunology Service, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, West Midlands, B15 2TT, UK. a.m.shields@bham.ac.uk.
2
Department of Pharmacology and Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
3
Department of Clinical Immunology, John Radcliffe Hospital, Oxford, OX3 9DU, UK.
4
NIHR Oxford Biomedical Research Centre, Oxford, UK.
5
Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.

Abstract

Germline gain-of-function mutations in CARD11 lead to the primary immunodeficiency, B cell expansion with NF-κB, and T cell anergy (BENTA). Herein, we report the case of a girl, presenting at 2 years of age with lymphocytosis and splenomegaly in whom a novel, in-frame, three base pair deletion in CARD11 was identified resulting in the deletion of a single lysine residue (K215del) from the coiled-coil domain. In vitro functional assays demonstrated that this variant leads to a subtle increase in baseline NF-κB signaling and impaired proliferative responses following T cell receptor and mitogenic stimulation. Previously reported immunological defects associated with BENTA appear mild in our patient who is now 6 years of age; a B cell lymphocytosis and susceptibility to upper respiratory tract infections persist; however, she has broad, sustained responses to protein-polysaccharide conjugate vaccines and displays normal proliferative responses to ex vivo T cell stimulation.

KEYWORDS:

BENTA; CARD11; Primary immunodeficiency

PMID:
31897776
DOI:
10.1007/s10875-019-00729-x

Supplemental Content

Full text links

Icon for Springer
Loading ...
Support Center