title: Interferon-gamma reduces the proliferation of M. tuberculosis within macrophages from a patient with a novel hypomorphic NEMO mutation.
abstract: X-linked ectodermal dysplasia with immunodeficiency (XL-EDA-ID) is caused by mutations in the nuclear factor-kappa B essential modulator (NEMO) gene. Here, we report the clinical and genetic features of a XL-EDA-ID patient who developed bacillus Calmette-Guérin infection. Patient lymphocytes failed to degrade IκB-α, and sequencing of NEMO identified the novel mutation c.1238A>C/p.H413P. Furthermore, patient monocyte-derived macrophages ingested Mycobacterium tuberculosis normally, but failed to control the intracellular proliferation of bacilli, a defect which was improved in the presence of interferon-gamma (IFN-γ). This work expands the genetic spectrum of XL-EDA-ID and demonstrates improvement in macrophage function in a NEMO-deficient patient by IFN-γ.
authors.affiliation: Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.|Department of Microbiology, Kohat University of Science and Technology, Kohat, Pakistan.
authors.forename: Taj Ali
authors.initials: TA
authors.lastname: Khan
authors.affiliation: Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Lena Friederike
authors.initials: LF
authors.lastname: Schimke
authors.affiliation: Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Eduardo Pinheiro
authors.initials: EP
authors.lastname: Amaral
authors.affiliation: Basic Science Research Department, Shaukat Khanum Memorial Cancer Hospital & Research Centre, Lahore, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ishfaq
authors.affiliation: Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Caio César
authors.initials: CC
authors.lastname: Barbosa Bonfim
authors.affiliation: Department of Microbiology, Kohat University of Science and Technology, Kohat, Pakistan.
authors.forename: Hazir
authors.initials: H
authors.lastname: Rahman
authors.affiliation: Laboratory of Biochemistry and Biophysics, Butantan Institute, Sao Paulo, Brazil.
authors.forename: Asif
authors.initials: A
authors.lastname: Iqbal
authors.affiliation: Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Maria Regina
authors.initials: MR
authors.lastname: D'Império Lima
authors.affiliation: Division of Allergy-Immunology and Rheumatology, Department of Pediatrics, Federal University of São Paulo, SP, Brazil.
authors.forename: Beatriz Tavares
authors.initials: BT
authors.lastname: Costa Carvalho
authors.affiliation: Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.|Department of Rheumatology, University of Lübeck, Lübeck, Germany.
authors.forename: Otavio
authors.initials: O
authors.lastname: Cabral-Marques
authors.affiliation: Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Antonio
authors.initials: A
authors.lastname: Condino-Neto
mesh_terms: D004476:Ectodermal Dysplasia / Q000188:drug therapy* / Q000276:immunology; D040181:Genetic Diseases, X-Linked / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000188:drug therapy* / Q000276:immunology; D007223:Infant; D007371:Interferon-gamma / Q000494:pharmacology / Q000627:therapeutic use*; D008264:Macrophages / Q000382:microbiology*; D008297:Male; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D000081207:Primary Immunodeficiency Diseases; D011994:Recombinant Proteins / Q000627:therapeutic use
chemical_list: D011994:Recombinant Proteins; D007371:Interferon-gamma
keywords: BCGitis; NEMO; ectodermal dysplasia