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Lenz, D.* ; Pahl, J.* ; Hauck, F.* ; Alameer, S.* ; Balasubramanian, M.* ; Baric, I.* ; Boy, N.* ; Church, J.A.* ; Crushell, E.* ; Dick, A.* ; Distelmaier, F.* ; Gujar, J.* ; Indolfi, G.* ; Lurz, E.* ; Peters, B.* ; Schwerd, T.* ; Serranti, D.* ; Kölker, S.* ; Klein, C.* ; Hoffmann, G.F.* ; Prokisch, H. ; Greil, J.* ; Cerwenka, A.* ; Giese, T.* ; Staufner, C.*

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

J. Clin. Immunol., DOI: 10.1007/s10875-021-01110-7 (2021)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter B Cell Deficiency ; Familial Hemophagocytic Lymphohistiocytosis ; Inborn Error Of Immunity ; Nbas ; Nk Cell Deficiency ; Vesicle Trafficking; Acute Liver-failure; Mutations; Diagnosis; Disease; Immunodeficiency; Mechanisms; Guidelines; Spectrum; Gene
ISSN (print) / ISBN 0271-9142
e-ISSN 1573-2592
Zeitschrift Journal of Clinical Immunology
Verlag Springer
Verlagsort New York, NY
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Human Genetics (IHG)
Förderungen Deutsche Leberstiftung
Jeffrey Model Foundation
SFB/TRR 179
German Research Foundation (DFG)
State of Baden-Wurttemberg Foundation special program "Angioformatics single cell platform"
German Centre for Infection Research (DZIF)
Else Kroner-Fresenius Stiftung (EKFS)
German Federal Ministry of Education and Research (BMBF)
SFB1366
SPP 1937
Dietmar Hopp Foundation, St. LeonRot, Germany