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 recep tor 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 my cobacteria, poor granuloma formation, and a fatal outcome in childhood, Par tial IFN-gamma R1 deficiency is associated with a milder histopathologic an d clinical phenotype, Cells from a 20-year-old healthy person with a histor y of curable infections due to bacille Calmette-Guerin and Mycobacterium ab scessus and mature granulomas in childhood were investigated, There was a h omozygous nucleotide substitution in IFNGR2, causing an amino acid substitu tion in the extracellular region of the encoded receptor, Cell surface IFN- gamma R2 were detected by flow cytometry, Cellular responses to IFN-gamma w ere 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.