Dataset Information

Acquired and Innate Immunity Impairment and Severe Disseminated Mycobacterium genavense Infection in a Patient With a NF-?B1 Deficiency.

ABSTRACT: Background: NF-?B1 is a master regulator of both acquired and innate responses. NFKB1 loss-of-function mutations elicit a wide clinical phenotype with asymptomatic individuals at one end of the spectrum and patients with common variable immunodeficiency, combined immunodeficiency or autoinflammation at the other. Impairment of acquired and innate immunity and disseminated Mycobacterium genavense infection expands the clinical and immunological phenotype of NF-?B1 deficiency. Objective: Functional and molecular characterization of a patient with a novel phenotype of NF-?B1 deficiency. Methods: Circulating T, B, dendritic cell subsets and innate or unconventional T-cells were quantified. The cytokine production in stimulated whole blood samples was assessed and molecular characterization by next generation sequencing and gene expression assays were also performed. Results: We report a patient presenting with features of combined immunodeficiency (CID) and disseminated Mycobacterium genavense infection. Sequencing of genomic DNA identified a novel synonymous mutation (c.705G > A) in NFKB1 gene which resulted in exon 8 skipping and haploinsufficiency of the NF-?B1 subunit p50. The susceptibility to atypical mycobacterial infection has not been previously reported and may be the result of a dendritic cell deficiency. A selective deficiency of circulating follicular helper T (cTFH) cells responsible for mediating the differentiation of naive B cells into memory and plasma cells was also present in the patient. It could affect the maturation of innate or unconventional T cells where NF-?B1 could also be involved. Conclusion: These findings showed that the role of NF-?B1 in humans could be critical for the development of acquired and innate immunity and further highlights the role of human T cells in anti-mycobacterial immunity.

SUBMITTER: Gonzalez-Granado LI

PROVIDER: S-EPMC6362422 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Acquired and Innate Immunity Impairment and Severe Disseminated Mycobacterium genavense Infection in a Patient With a NF-κB1 Deficiency.

Gonzalez-Granado Luis Ignacio LI Ruiz-García Raquel R Blas-Espada Javier J Moreno-Villares José Manuel JM Germán-Diaz Marta M López-Nevado Marta M Paz-Artal Estela E Toldos Oscar O Rodriguez-Gil Yolanda Y de Inocencio Jaime J Domínguez-Pinilla Nerea N Allende Luis M LM

Frontiers in immunology 20190129

Background: NF-κB1 is a master regulator of both acquired and innate responses. NFKB1 loss-of-function mutations elicit a wide clinical phenotype with asymptomatic individuals at one end of the spectrum and patients with common variable immunodeficiency, combined immunodeficiency or autoinflammation at the other. Impairment of acquired and innate immunity and disseminated Mycobacterium genavense infection expands the clinical and immunological phenotype of NF-κB1 deficiency. ...[more]

PMID: 30761159

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Project description:BackgroundSarcoidosis is a systemic inflammatory disease that is characterized by non-caseating epithelioid-cell granulomas upon histology. However, similar histological findings may also be seen with certain infections. Thus, differentiation from infection is pivotal to ensure appropriate treatment. Here, we present a case of a disseminated infection with Mycobacterium genavense owing to an interleukin 12 receptor subunit beta 1 (IL-12Rβ1) associated immunodeficiency in a previously healthy female who was initially misdiagnosed with sarcoidosis. M. genavense is a nontuberculous mycobacterium which can cause lymphadenopathy, gastrointestinal and bone marrow infiltration in immunocompromised patients. With this case report we aim to highlight that an infection with M. genavense on the ground of a genetic defect of mycobacterial immune control may represent a rare differential diagnosis of sarcoidosis.Case presentationA 31-year-old female was referred to our hospital with progressive lymphadenopathy, hepatosplenomegaly, pancytopenia and systemic inflammation. She had previously been evaluated for generalized lymphadenopathy in another hospital. At that time, lymph node biopsies had revealed sarcoid-like lesions and a systemic corticosteroid treatment was initiated based on a putative diagnosis of sarcoidosis. When her condition worsened, she was transferred to our university clinic, where the diagnosis of disseminated M. genavense infection owing to an inborn interferonopathy was made. Her family history revealed that her brother had also suffered from IL-12Rβ1 deficiency and had died from a systemic infection with M. genavense at the age of 21. The patient received antimycobacterial treatment combined with subcutaneous type I interferon, which eventually led to a gradual improvement over the next months.ConclusionsDifferentiating between sarcoidosis and sarcoid-like lesions secondary to infections may be challenging, especially when pathogens are difficult to detect or not expected in an apparently immunocompetent patient. Patients with IL-12Rβ1-associated immunodeficiency may be asymptomatic until adulthood, and disseminated M. genavense infection on the grounds of an IL-12Rβ1-associated immunodeficiency may represent a rare differential diagnosis of sarcoidosis.

Dataset Information

Acquired and Innate Immunity Impairment and Severe Disseminated Mycobacterium genavense Infection in a Patient With a NF-?B1 Deficiency.

Publications

Acquired and Innate Immunity Impairment and Severe Disseminated <i>Mycobacterium genavense</i> Infection in a Patient With a NF-κB1 Deficiency.

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