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

Area of Science:

• Immunology
• Genetics
• Cell Biology

Background:

• Biallelic pathogenic NBAS variants lead to a multisystem disorder with varied clinical features.
• NBAS-associated disease impacts both innate and adaptive immune cells.
• Understanding these immune alterations is crucial for managing NBAS deficiency.

Observation:

• Fifteen NBAS-deficient patients underwent immunophenotyping to identify immune system changes.
• Reduced numbers of mature CD56^dim natural killer (NK) cells were observed.
• Naïve B cell numbers were decreased, correlating with hypogammaglobulinemia.

Findings:

• NBAS deficiency results in dysfunctional NK cells with impaired activation and degranulation.
• NBAS plays an intrinsic role in cytotoxic granule release by NK cells.
• Impaired NK cell function is reversible with in vitro IL-2 pre-activation.
• Adaptive humoral immunity is compromised in NBAS-deficient individuals.

Implications:

• Pathogenic NBAS variants are linked to significant immune system defects.
• The findings highlight a crucial role for NBAS in immune cell function.
• This research provides insights into the pathophysiology of NBAS-associated disease.