NBAS Variants Are Associated with Quantitative and Qualitative NK and B Cell Deficiency

J Clin Immunol. 2021 Nov;41(8):1781-1793. doi: 10.1007/s10875-021-01110-7. Epub 2021 Aug 13.


Purpose: Biallelic pathogenic NBAS variants manifest as a multisystem disorder with heterogeneous clinical phenotypes such as recurrent acute liver failure, growth retardation, and susceptibility to infections. This study explores how NBAS-associated disease affects cells of the innate and adaptive immune system.

Methods: Clinical and laboratory parameters were combined with functional multi-parametric immunophenotyping methods in fifteen NBAS-deficient patients to discover possible alterations in their immune system.

Results: Our study revealed reduced absolute numbers of mature CD56dim natural killer (NK) cells. Notably, the residual NK cell population in NBAS-deficient patients exerted a lower potential for activation and degranulation in response to K562 target cells, suggesting an NK cell-intrinsic role for NBAS in the release of cytotoxic granules. NBAS-deficient NK cell activation and degranulation was normalized upon pre-activation by IL-2 in vitro, suggesting that functional impairment was reversible. In addition, we observed a reduced number of naïve B cells in the peripheral blood associated with hypogammaglobulinemia.

Conclusion: In summary, we demonstrate that pathogenic biallelic variants in NBAS are associated with dysfunctional NK cells as well as impaired adaptive humoral immunity.

Keywords: B cell deficiency; NBAS; NK cell deficiency; familial hemophagocytic lymphohistiocytosis; inborn error of immunity; vesicle trafficking.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • B-Lymphocytes / immunology*
  • Child
  • Child, Preschool
  • Cytokines / immunology
  • Gene Expression
  • Genotype
  • Humans
  • Immunologic Deficiency Syndromes / genetics*
  • Immunologic Deficiency Syndromes / immunology*
  • Infant
  • Killer Cells, Natural / immunology*
  • Leukocyte Count
  • Neoplasm Proteins / deficiency
  • Neoplasm Proteins / genetics*
  • Phenotype
  • Young Adult


  • Cytokines
  • NBAS protein, human
  • Neoplasm Proteins