NBAS variants are associated with quantitative and ualitative NK and B Cell deficiency

Medientyp: E-Artikel

Titel: NBAS variants are associated with quantitative and ualitative NK and B Cell deficiency

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

Erschienen: 13 August 2021

Sprache: Englisch

DOI: 10.1007/s10875-021-01110-7

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Beschreibung: 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 C D56dim 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.

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