Partial interferon-gamma 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)-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.
Döffinger
R
R
Institut National de la Santé et de la Recherche Médicale (INSERM) U429, Paris, France.
Jouanguy
E
E
Dupuis
S
S
Fondanèche
M C
MC
Stephan
J L
JL
Emile
J F
JF
Lamhamedi-Cherradi
S
S
Altare
F
F
Pallier
A
A
Barcenas-Morales
G
G
Meinl
E
E
Krause
C
C
Pestka
S
S
Schreiber
R D
RD
Novelli
F
F
Casanova
J L
JL
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
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