NBAS Variants Are Associated with Quantitative and Qualitative NK and B Cell Deficiency.
J Clin Immunol
; 41(8): 1781-1793, 2021 11.
Article
in En
| MEDLINE
| ID: mdl-34386911
ABSTRACT
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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
B-Lymphocytes
/
Killer Cells, Natural
/
Immunologic Deficiency Syndromes
/
Neoplasm Proteins
Type of study:
Qualitative_research
/
Risk_factors_studies
Limits:
Adolescent
/
Adult
/
Child
/
Child, preschool
/
Humans
/
Infant
Language:
En
Journal:
J Clin Immunol
Year:
2021
Document type:
Article
Affiliation country:
Germany