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Clin Immunol ; 195: 49-58, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30063981


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-1ß, 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.

Linfócitos B/fisiologia , Imunodeficiência de Variável Comum/imunologia , Gastroenteropatias/imunologia , NF-kappa B/genética , Deleção de Sequência/genética , Células Th1/fisiologia , Adolescente , Adulto , Agamaglobulinemia , Células Cultivadas , Imunodeficiência de Variável Comum/genética , Citocinas/metabolismo , Feminino , Gastroenteropatias/genética , Humanos , Mediadores da Inflamação/metabolismo , Masculino , Proteína Adaptadora de Sinalização NOD2/genética , Infecções Respiratórias , Adulto Jovem