Th1-skewed profile and excessive production of proinflammatory cytokines in a NFKB1-deficient patient with CVID and severe gastrointestinal manifestations

Bibliographische Detailangaben
Veröffentlicht in:	Clinical immunology (Orlando, Fla.). - 1999. - 195(2018) vom: 15. Okt., Seite 49-58
1. Verfasser:	Dieli-Crimi, Romina (VerfasserIn)
Weitere Verfasser:	Martínez-Gallo, Mónica, Franco-Jarava, Clara, Antolin, Maria, Blasco, Laura, Paramonov, Ida, Semidey, Maria E, Álvarez Fernández, Antoni, Molero, Xavier, Velásquez, Julio, Martín-Nalda, Andrea, Pujol-Borrell, Ricardo, Colobran, Roger
Format:	Online-Aufsatz
Sprache:	English
Veröffentlicht:	2018
Zugriff auf das übergeordnete Werk:	Clinical immunology (Orlando, Fla.)
Schlagworte:	Case Reports Journal Article Research Support, Non-U.S. Gov't Autoinflammation Common Variable Immunodeficiency Enteropathy NF-κB pathway NFKB1 NOD2 Next Generation Sequencing mehr... Primary Immunodeficiency Th1 cells Cytokines Inflammation Mediators NF-kappa B NOD2 protein, human Nod2 Signaling Adaptor Protein

Beschreibung
Zusammenfassung:	Copyright © 2018 Elsevier Inc. All rights reserved. Monoallelic loss-of-function mutations in NFKB1 were recently recognized as the most common monogenic cause of common variable immunodeficiency (CVID). The prototypic clinical phenotype of NFKB1-deficient patients includes common CVID features, such as hypogammaglobulinaemia and sinopulmonary infections, plus other highly variable individual manifestations. Here, we describe a patient with a profound CVID phenotype and severe gastrointestinal manifestations, including chronic and recurrent diarrhoea. Using an NGS customized panel of 323 genes related to primary immunodeficiencies, we identified a novel monoallelic loss-of-function mutation in NFKB1 leading to a truncated protein (c.1149delT/p.Gly384Glu ∗ 48). Interestingly, we also found a rare variant in NOD2 previously associated with Crohn's disease (p.His352Arg). Our patient had hypogammaglobulinaemia with a small number of B cells, most of which were naïve. The most noteworthy findings included marked skewing towards a Th1 phenotype in peripheral blood T cells and excessive production of proinflammatory cytokines (IL-1β, TNFα). The patient's 6-year-old daughter, a carrier of the NFKB1 mutation, is clinically asymptomatic, but has started to show cellular and molecular changes. This case of NFKB1 deficiency appears to be a combination of immunodeficiency and a hyperinflammatory state. The current situation of the patient's daughter provides a glimpse of the preclinical phase of the condition
Beschreibung:	Date Completed 27.08.2019 Date Revised 27.08.2019 published: Print-Electronic Citation Status MEDLINE
ISSN:	1521-7035
DOI:	10.1016/j.clim.2018.07.015