Partial interferon-gamma 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)-gamma receptor components, the ligand-binding IFN-gamma R1 chain and the signaling IFN-gamma R2 chain, is invariably associated with early-onset infection caused by bacille Calmeete-Guerin vaccines and/or environmental nontuberculous mycobacteria, poor granuloma formation, and a fatal outcome in childhood, Partial IFN-gamma R1 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-gamma R2 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-gamma R2 deficiency in humans.