TY - JOUR
T1 - Th1-skewed profile and excessive production of proinflammatory cytokines in a NFKB1-deficient patient with CVID and severe gastrointestinal manifestations
AU - Dieli-Crimi, Romina
AU - Martínez-Gallo, Mónica
AU - Franco-Jarava, Clara
AU - Antolin, Maria
AU - Blasco, Laura
AU - Paramonov, Ida
AU - Semidey, Maria E.
AU - Álvarez Fernández, Antoni
AU - Molero, Xavier
AU - Velásquez, Julio
AU - Martín-Nalda, Andrea
AU - Pujol-Borrell, Ricardo
AU - Colobran, Roger
PY - 2018/10/1
Y1 - 2018/10/1
N2 - © 2018 Elsevier Inc. 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.
AB - © 2018 Elsevier Inc. 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.
KW - Autoinflammation
KW - Common Variable Immunodeficiency
KW - Enteropathy
KW - Next Generation Sequencing
KW - NF-κB pathway
KW - NFKB1
KW - NOD2
KW - Primary Immunodeficiency
KW - Th1 cells
U2 - 10.1016/j.clim.2018.07.015
DO - 10.1016/j.clim.2018.07.015
M3 - Article
C2 - 30063981
VL - 195
SP - 49
EP - 58
JO - Clinical Immunology
JF - Clinical Immunology
SN - 1521-6616
ER -