Naslov
NBAS variants are associated with quantitative and qualitative NK and B cell deficiency

Autori
Lenz, Dominic ; Pahl, Jens ; Hauck, Fabian ; Alameer, Seham ; Balasubramanian, Meena ; Barić, Ivo ; Boy, Nikolas ; Church, Joseph A. ; Crushell, Ellen ; Dick, Anke ; Distelmaier, Felix ; Gujar, Jidnyasa ; Indolfi, Giuseppe ; Lurz, Eberhard ; Peters, Bianca ; Schwerd, Tobias ; Serranti, Daniele ; Kölker, Stefan ; Klein, Christoph ; Hoffmann, Georg F. ; Prokisch, Holger ; Greil, Johann ; Cerwenka, Adelheid ; Giese, Thomas ; Staufner, Christian

Izvornik
Journal of clinical immunology (0271-9142) 41 (2021), 8; 1781-1793

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
B cell deficiency ; NBAS ; NK cell deficiency ; familial hemophagocytic lymphohistiocytosis ; inborn error of immunity ; vesicle trafficking

Sažetak
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.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti

POVEZANOST RADA