Partial Interferon-γ Receptor Signaling Chain Deficiency in a Patient with Bacille Calmette-Guérin and Mycobacterium abscessus Infection

Complete deficiency of either of the two human interferon (IFN)-γ receptor components, the ligand-binding IFN-γR1 chain and the signaling IFN-γR2 chain, is invariably associated with early-onset infection caused by bacille Calmette-Guérin vaccines and/or environmental nontuberculous mycobacteria, po...

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Bibliographic Details
Published in:The Journal of infectious diseases 2000-01, Vol.181 (1), p.379-384
Main Authors: Döfflnger, Rainer, Jouanguy, Emmanuelle, Dupuis, Stéphanie, Fondanèche, Marie-Claude, Stephan, Jean-Louis, Emile, Jean-François, Lamhamedi-Cherradi, Salma, Altare, Frédéric, Pallier, Annaïck, Barcenas-Morales, Gabriela, Meinl, Edgar, Krause, Christopher, Pestka, Sidney, Schreiber, Robert D., Novelli, Francesco, Casanova, Jean-Laurent
Format: Article
Language:English
Subjects:
Adult
Alleles
B lymphocytes
bacille Calmette-Guerin
BCG Vaccine - adverse effects
Cell lines
Concise Communications
Cytometry
DNA-Binding Proteins - metabolism
Female
Fibroblasts
Genetic mutation
Genotype
Granuloma
HLA-DR Antigens - metabolism
Homozygote
Humans
Infections
Interferon gamma Receptor
Molecules
Mycobacterium abscessus
Mycobacterium bovis - immunology
Mycobacterium bovis - pathogenicity
Mycobacterium Infections - immunology
Pedigree
Phenotype
Point Mutation
Receptors
Receptors, Interferon - genetics
Receptors, Interferon - metabolism
Signal Transduction
STAT1 Transcription Factor
Trans-Activators - metabolism
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Summary:Complete deficiency of either of the two human interferon (IFN)-γ receptor components, the ligand-binding IFN-γR1 chain and the signaling IFN-γR2 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-γR1 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-γR2 were detected by flow cytometry. Cellular responses to IFN-γ were impaired but not abolished. Transfection with the wild-type IFNGR2 gene restored full responsiveness to IFN-γ. This is the first demonstration of partial IFN-γR2 deficiency in humans.
ISSN:0022-1899
1537-6613
DOI:10.1086/315197