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Th1-skewed profile and excessive production of proinflammatory cytokines in a NFKB1-deficient patient with CVID and severe gastrointestinal manifestations.
- Source :
-
Clinical immunology (Orlando, Fla.) [Clin Immunol] 2018 Oct; Vol. 195, pp. 49-58. Date of Electronic Publication: 2018 Jul 29. - Publication Year :
- 2018
-
Abstract
- 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.<br /> (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Subjects :
- Adolescent
Adult
Agammaglobulinemia
Cells, Cultured
Common Variable Immunodeficiency genetics
Cytokines metabolism
Female
Gastrointestinal Diseases genetics
Humans
Inflammation Mediators metabolism
Male
Nod2 Signaling Adaptor Protein genetics
Respiratory Tract Infections
Young Adult
B-Lymphocytes physiology
Common Variable Immunodeficiency immunology
Gastrointestinal Diseases immunology
NF-kappa B genetics
Sequence Deletion genetics
Th1 Cells physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1521-7035
- Volume :
- 195
- Database :
- MEDLINE
- Journal :
- Clinical immunology (Orlando, Fla.)
- Publication Type :
- Academic Journal
- Accession number :
- 30063981
- Full Text :
- https://doi.org/10.1016/j.clim.2018.07.015