title: Partial interferon-gamma receptor signaling chain deficiency in a patient with bacille Calmette-Guérin and Mycobacterium abscessus infection.
abstract: Complete deficiency of either of the two human interferon (IFN)-gamma receptor components, the ligand-binding IFN-gammaR1 chain and the signaling IFN-gammaR2 chain, is invariably associated with early-onset infection caused by bacille Calmette-Guérin vaccines and/or environmental nontuberculous mycobacteria, poor granuloma formation, and a fatal outcome in childhood. Partial IFN-gammaR1 deficiency is associated with a milder histopathologic and clinical phenotype. Cells from a 20-year-old healthy person with a history of curable infections due to bacille Calmette-Guérin and Mycobacterium abscessus and mature granulomas in childhood were investigated. There was a homozygous nucleotide substitution in IFNGR2, causing an amino acid substitution in the extracellular region of the encoded receptor. Cell surface IFN-gammaR2 were detected by flow cytometry. Cellular responses to IFN-gamma were impaired but not abolished. Transfection with the wild-type IFNGR2 gene restored full responsiveness to IFN-gamma. This is the first demonstration of partial IFN-gammaR2 deficiency in humans.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) U429, Paris, France.
authors.forename: R
authors.initials: R
authors.lastname: Döffinger
authors.forename: E
authors.initials: E
authors.lastname: Jouanguy
authors.forename: S
authors.initials: S
authors.lastname: Dupuis
authors.forename: M C
authors.initials: MC
authors.lastname: Fondanèche
authors.forename: J L
authors.initials: JL
authors.lastname: Stephan
authors.forename: J F
authors.initials: JF
authors.lastname: Emile
authors.forename: S
authors.initials: S
authors.lastname: Lamhamedi-Cherradi
authors.forename: F
authors.initials: F
authors.lastname: Altare
authors.forename: A
authors.initials: A
authors.lastname: Pallier
authors.forename: G
authors.initials: G
authors.lastname: Barcenas-Morales
authors.forename: E
authors.initials: E
authors.lastname: Meinl
authors.forename: C
authors.initials: C
authors.lastname: Krause
authors.forename: S
authors.initials: S
authors.lastname: Pestka
authors.forename: R D
authors.initials: RD
authors.lastname: Schreiber
authors.forename: F
authors.initials: F
authors.lastname: Novelli
authors.forename: J L
authors.initials: JL
authors.lastname: Casanova
mesh_terms: D000328:Adult; D001500:BCG Vaccine / Q000009:adverse effects*; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D005838:Genotype; D006684:HLA-DR Antigens / Q000378:metabolism; D006720:Homozygote; D006801:Humans; D009164:Mycobacterium Infections / Q000276:immunology*; D009163:Mycobacterium bovis / Q000276:immunology / Q000472:pathogenicity; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation; D017471:Receptors, Interferon / Q000235:genetics* / Q000378:metabolism*; D050794:STAT1 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism; D000096743:Interferon gamma Receptor
chemical_list: D001500:BCG Vaccine; D004268:DNA-Binding Proteins; D006684:HLA-DR Antigens; D017471:Receptors, Interferon; D050794:STAT1 Transcription Factor; D015534:Trans-Activators; D000096743:Interferon gamma Receptor; C494079:STAT1 protein, human