Partial interferon-γ receptor signaling chain deficiency in a patient with bacille Calmette-Guerin and Mycobacterium abscessus infection

Rainer Döffinger, Emmanuelle Jouanguy, Stéphanie Dupuis, Marie Claude Fondanèche, Jean Louis Stephan, Jean François Emile, Salma Lamhamedi-Cherradi, Frédéric Altare, Annaïck Pallier, Gabriela Barcenas-Morales, Edgar Meinl, Christopher Krause, Sidney Pestka, Robert D. Schreiber, Francesco Novelli, Jean Laurent Casanova

Research output: Contribution to journalArticle

153 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)379-384
Number of pages6
JournalJournal of Infectious Diseases
Volume181
Issue number1
DOIs
StatePublished - Jan 26 2000

Fingerprint Dive into the research topics of 'Partial interferon-γ receptor signaling chain deficiency in a patient with bacille Calmette-Guerin and Mycobacterium abscessus infection'. Together they form a unique fingerprint.

  • Cite this

    Döffinger, R., Jouanguy, E., Dupuis, S., Fondanèche, M. C., Stephan, J. L., Emile, J. F., Lamhamedi-Cherradi, S., Altare, F., Pallier, A., Barcenas-Morales, G., Meinl, E., Krause, C., Pestka, S., Schreiber, R. D., Novelli, F., & Casanova, J. L. (2000). Partial interferon-γ receptor signaling chain deficiency in a patient with bacille Calmette-Guerin and Mycobacterium abscessus infection. Journal of Infectious Diseases, 181(1), 379-384. https://doi.org/10.1086/315197