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

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...

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Main Authors: Lenz, Dominic (Author) , Pahl, Jens (Author) , Hauck, Fabian (Author) , Alameer, Seham (Author) , Balasubramanian, Meena (Author) , Baric, Ivo (Author) , Boy, Nikolas (Author) , Church, Joseph A. (Author) , Crushell, Ellen (Author) , Dick, Anke (Author) , Distelmaier, Felix (Author) , Gujar, Jidnyasa (Author) , Indolfi, Giuseppe (Author) , Lurz, Eberhard (Author) , Peters, Bianca (Author) , Schwerd, Tobias (Author) , Serranti, Daniele (Author) , Kölker, Stefan (Author) , Klein, Christoph (Author) , Hoffmann, Georg F. (Author) , Prokisch, Holger (Author) , Greil, Johann (Author) , Cerwenka, Adelheid (Author) , Giese, Thomas (Author) , Staufner, Christian (Author)
Format: Article (Journal)
Language:English
Published: 13 August 2021
In: Journal of clinical immunology
Year: 2021, Volume: 41, Issue: 8, Pages: 1781-1793
ISSN:1573-2592
DOI:10.1007/s10875-021-01110-7
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1007/s10875-021-01110-7
Verlag, kostenfrei, Volltext: https://link.springer.com/10.1007/s10875-021-01110-7
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Author Notes:Dominic Lenz, Jens Pahl, Fabian Hauck, Seham Alameer, Meena Balasubramanian, Ivo Baric, Nikolas Boy, Joseph A. Church, Ellen Crushell, Anke Dick, Felix Distelmaier, Jidnyasa Gujar, Giuseppe Indolfi, Eberhard Lurz, Bianca Peters, Tobias Schwerd, Daniele Serranti, Stefan Kölker, Christoph Klein, Georg F. Hoffmann, Holger Prokisch, Johann Greil, Adelheid Cerwenka, Thomas Giese, Christian Staufner
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Summary: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.
Item Description:Gesehen am 21.08.2023
Physical Description:Online Resource
ISSN:1573-2592
DOI:10.1007/s10875-021-01110-7

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