Inherited interleukin 12 deficiency in a child with bacille Calmette-Guérin and Salmonella enteritidis disseminated infection

J Clin Invest. 1998 Dec 15;102(12):2035-40. doi: 10.1172/JCI4950.


Interferon-gamma receptor ligand-binding chain (IFN-gammaR1) or signaling chain (IFN-gammaR2) deficiency, like interleukin 12 receptor beta1 chain (IL-12Rbeta1) deficiency, predispose to severe infections due to poorly virulent mycobacteria and salmonella. A child with bacille Calmette-Guérin and Salmonella enteritidis infection was investigated. Mutations in the genes for IFN-gammaR1, IFN-gammaR2, IL-12Rbeta1, and other molecules implicated in IL-12- or IFN-gamma-mediated immunity were sought. A large homozygous deletion within the IL-12 p40 subunit gene was found, precluding expression of functional IL-12 p70 cytokine by activated dendritic cells and phagocytes. As a result, IFN-gamma production by lymphocytes was markedly impaired. This is the first discovered human disease resulting from a cytokine gene defect. It suggests that IL-12 is essential to and appears specific for protective immunity to intracellular bacteria such as mycobacteria and salmonella.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • BCG Vaccine / immunology*
  • Bacterial Infections / genetics*
  • Base Sequence
  • Child
  • Female
  • Genetic Complementation Test
  • Granuloma / pathology
  • Humans
  • Interferon-gamma / metabolism
  • Interleukin-12 / deficiency
  • Interleukin-12 / genetics*
  • Leukocytes
  • Lymph Nodes / pathology
  • Molecular Sequence Data
  • Mycobacterium / immunology
  • Mycobacterium / pathogenicity
  • Pedigree
  • Salmonella enteritidis / immunology
  • Salmonella enteritidis / pathogenicity*
  • Sequence Analysis, DNA
  • Sequence Deletion / genetics
  • Transfection / genetics


  • BCG Vaccine
  • Interleukin-12
  • Interferon-gamma