Partial Interferon‐γ Receptor Signaling Chain Deficiency in a Patient with Bacille Calmette‐Guérin andMycobacterium abscessusInfection

• DOI: 10.1086/315197
• Publication Date: 2002-07-26T18:58:45Z
• Authors: Rainer Döffinger; Emmanuelle Jouanguy; Stéphanie Dupuis; Marie‐Claude Fond...; Jean‐Louis Stephan; Jean‐François Emile; Salma Lamhamedi‐C...; Frédéric Altare; Annaïck Pallier; Gabriela Barcenas...; Edgar Meinl; Christopher Krause; Sidney Pestka; Robert D. Schreiber; Francesco Novelli; Jean‐Laurent Casa...
• Keywords: Adult; Mycobacterium Infections; 0303 health sciences; Genotype; Homozygote; HLA-DR Antigens; Mycobacterium bovis; Pedigree; 3. Good health; DNA-Binding Proteins; 03 medical and health sciences; Phenotype; STAT1 Transcription Factor; BCG Vaccine; Trans-Activators; Humans; Point Mutation; Female; Receptors, Interferon; Signal Transduction; Interferon gamma Receptor

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.