A novel, heterozygous three base-pair deletion in CARD11 results in B cell expansion with NF-κB and T cell anergy disease

Research output: Contribution to journalLetter

Authors

  • Bradly Bauman
  • Chantal Hargreaves
  • Andrew Pollard
  • Andrew Snow
  • Smita Y Patel

Colleges, School and Institutes

External organisations

  • Department of Pharmacology and Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA
  • NIHR Oxford Biomedical Research Centre, Oxford, UK
  • Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, Oxford, United Kingdom.

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

Details

Original languageEnglish
JournalJournal of Clinical Immunology
Early online date2 Jan 2020
Publication statusE-pub ahead of print - 2 Jan 2020

Keywords

  • CARD11, BENTA, Primary immunodeficiency

ASJC Scopus subject areas