Pathogenic NFKB2 variant in the ankyrin repeat domain (R635X) causes a variable antibody deficiency

Pathogenic NFKB2 variant in the ankyrin repeat domain (R635X) causes a variable antibody deficiency

Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

Bibliographische Detailangaben
Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 203(2019) vom: 03. Juni, Seite 23-27
1. Verfasser: Tuijnenburg, Paul (VerfasserIn)
Weitere Verfasser: Lango Allen, Hana, de Bree, Godelieve J, Savic, Sinisa, Jansen, Machiel H, Stockdale, Claire, Simeoni, Ilenia, Ten Berge, Ineke J M, van Leeuwen, Ester M M, NIHR BioResource, Thaventhiran, James E, Kuijpers, Taco W
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2019
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Case Reports Journal Article Research Support, Non-U.S. Gov't B cells Common variable immunodeficiency NFKB2 T cells CXCR5 protein, human NF-kappa B p52 Subunit NFKB2 protein, human Receptors, CXCR5
Beschreibung
Zusammenfassung:Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.
Genetic studies are identifying an increasing number of monogenic causes of Common Variable Immunodeficiency (CVID). Pathogenic variants in the C-terminus of NFKB2 have been identified in the subset of CVID patients whose immunodeficiency is associated with ectodermal dysplasia and central adrenal insufficiency. We describe 2 unrelated CVID pedigrees with 4 cases of pathogenic stop gain variants (c.1903C > T) in the ankyrin repeat domain (ARD) of NF-κB2, leading to a premature truncation of the protein at p.Arg635Term (R635X). By immunophenotyping and functional ex vivo B- and T-cell experiments we characterized the variant by reduced class-switched memory B-cell counts and immature plasmablasts, unable to produce IgG and IgA. Features of a poor proliferative T-cell response and reduced expansion of CD4+CXCR5+ T cells was only observed in the two clinically affected index cases without any clear clinical correlate. In conclusion, pathogenic stop variants in the ARD of NFKB2 can cause 'infection-only' CVID with an abnormal B-cell phenotype and a variable clinical penetrance
Beschreibung:Date Completed 02.04.2020
Date Revised 09.01.2021
published: Print-Electronic
Citation Status MEDLINE
ISSN:1521-7035
DOI:10.1016/j.clim.2019.03.010