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

Interferon-gamma receptor ligand-binding chain (IFN-gamma R1) or signaling chain (IFN-gamma R2) deficiency, like interleukin 12 receptor beta 1 chain (IL-12R beta 1) 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-gamma R1, IFN-gamma R2, IL-12R beta 1, 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.