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

Abstract

Interferon-γ, receptor ligand-binding chain (IFN-γR1) or signaling chain (IFN-γR2) deficiency, like interleukin 12 receptor β1 chain (IL- 12Rβ1) deficiency, predispose to severe infections due to poorly virulent mycobacteria and salmonella. A child with bacille Calmette-Guerin and Salmonella enteritidis infection was investigated. Mutations in the genes for IFN-γR1, IFN-γR2, IL-12Rβ1, and other molecules implicated in IL-12- or IFN-γ-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- γ 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.