ArticleThe Journal of experimental medicine2006
X-linked susceptibility to mycobacteria is caused by mutations in NEMO impairing CD40-dependent IL-12 production.
Article in The Journal of experimental medicine, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 130 papers, 2 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
130 citing papers in PubMed, 2 syntheses or guidelines pooled it, 277 citations in OpenAlex.
- Genetic, immunologic, and clinical features of 830 patients with Mendelian susceptibility to mycobacterial diseases (MSMD): A systematic review.The Journal of allergy and clinical immunology · 2024Pooled it
- An Updated Review on MSMD Research Globally and A Literature Review on the Molecular Findings, Clinical Manifestations, and Treatment Approaches in China.Frontiers in immunology · 2022Pooled it
- Value of allohaemagglutinins in the diagnosis of a polysaccharide antibody deficiency.Clinical and experimental immunology · 2015Trial
- CD40 ligand and interferon-γ induce an antimicrobial response against Mycobacterium tuberculosis in human monocytes.Immunology · 2013Trial
- Human inborn errors of the alternative NF-κB pathway.Journal of human immunity · 2026Review
- Mendelian susceptibility to mycobacterial disease: IFN-γ-driven immunity collapse underlies heterogeneous infections.Frontiers in immunology · 2026Review
- Pediatric ectodermal dysplasia with immunodeficiency caused by a hemizygousFrontiers in immunology · 2026Review
- Review
- Partial Loss of NEMO Function in a Female Carrier with No Incontinentia Pigmenti.Journal of clinical medicine · 2025Article
- Management of tuberculosis risk, screening and preventive therapy in patients with chronic autoimmune arthritis undergoing biotechnological and targeted immunosuppressive agents.Frontiers in immunology · 2025Review
- Atypical Mycobacterial Pneumonia in 2 Siblings with a Novel Hypomorphic NEMO/IKBKG Mutation.Turkish archives of pediatrics · 2024Article
- Interferon Gamma in Sickness Predisposing toBalkan medical journal · 2024Review
- Interferon-Science (New York, N.Y.) · 2024Review
- Diagnosis and Management of Infections in Patients with Mendelian Susceptibility to Mycobacterial Disease.Pathogens (Basel, Switzerland) · 2024Review
- Recombinant IFN-γ1b Treatment in a Patient with Inherited IFN-γ Deficiency.Journal of clinical immunology · 2024Article
- Host Susceptibility to Nontuberculous Mycobacterial Pulmonary Disease.Clinics in chest medicine · 2023Review
- Human MCTS1-dependent translation of JAK2 is essential for IFN-γ immunity to mycobacteria.Cell · 2023Article
- Novel mutations in CYBB Gene Cause X-linked chronic Granulomatous Disease in Pakistani patients.Italian journal of pediatrics · 2023Article
- Article
- Distinct Lymphocyte Immunophenotyping and Quantitative Anti-Interferon Gamma Autoantibodies in Taiwanese HIV-Negative Patients with Non-Tuberculous Mycobacterial Infections.Journal of clinical immunology · 2023Article
70 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
37 authors at 12 institutions in 9 countries.
Funding
Abstract
Germline mutations in five autosomal genes involved in interleukin (IL)-12-dependent, interferon (IFN)-gamma-mediated immunity cause Mendelian susceptibility to mycobacterial diseases (MSMD). The molecular basis of X-linked recessive (XR)-MSMD remains unknown. We report here mutations in the leucine zipper (LZ) domain of the NF-kappaB essential modulator (NEMO) gene in three unrelated kindreds with XR-MSMD. The mutant proteins were produced in normal amounts in blood and fibroblastic cells. However, the patients' monocytes presented an intrinsic defect in T cell-dependent IL-12 production, resulting in defective IFN-gamma secretion by T cells. IL-12 production was also impaired as the result of a specific defect in NEMO- and NF-kappaB/c-Rel-mediated CD40 signaling after the stimulation of monocytes and dendritic cells by CD40L-expressing T cells and fibroblasts, respectively. However, the CD40-dependent up-regulation of costimulatory molecules of dendritic cells and the proliferation and immunoglobulin class switch of B cells were normal. Moreover, the patients' blood and fibroblastic cells responded to other NF-kappaB activators, such as tumor necrosis factor-alpha, IL-1beta, and lipopolysaccharide. These two mutations in the NEMO LZ domain provide the first genetic etiology of XR-MSMD. They also demonstrate the importance of the T cell- and CD40L-triggered, CD40-, and NEMO/NF-kappaB/c-Rel-mediated induction of IL-12 by monocyte-derived cells for protective immunity to mycobacteria in humans.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.