Partial interferon-γ receptor signaling chain deficiency in a patient with bacille Calmette-Guerin 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-Guerin 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-Guerin 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.