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. 1998 Dec 15;102(12):2035–2040. doi: 10.1172/JCI4950

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

F Altare 1, D Lammas 1, P Revy 1, E Jouanguy 1, R Döffinger 1, S Lamhamedi 1, P Drysdale 1, D Scheel-Toellner 1, J Girdlestone 1, P Darbyshire 1, M Wadhwa 1, H Dockrell 1, M Salmon 1, A Fischer 1, A Durandy 1, J L Casanova 1, D S Kumararatne 1
PMCID: PMC509157  PMID: 9854038

Abstract

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.

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Selected References

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