title: Inherited interleukin 12 deficiency in a child with bacille Calmette-Guérin and Salmonella enteritidis disseminated infection.
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.
authors.affiliation: INSERM U429, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Altare
authors.forename: D
authors.initials: D
authors.lastname: Lammas
authors.forename: P
authors.initials: P
authors.lastname: Revy
authors.forename: E
authors.initials: E
authors.lastname: Jouanguy
authors.forename: R
authors.initials: R
authors.lastname: Döffinger
authors.forename: S
authors.initials: S
authors.lastname: Lamhamedi
authors.forename: P
authors.initials: P
authors.lastname: Drysdale
authors.forename: D
authors.initials: D
authors.lastname: Scheel-Toellner
authors.forename: J
authors.initials: J
authors.lastname: Girdlestone
authors.forename: P
authors.initials: P
authors.lastname: Darbyshire
authors.forename: M
authors.initials: M
authors.lastname: Wadhwa
authors.forename: H
authors.initials: H
authors.lastname: Dockrell
authors.forename: M
authors.initials: M
authors.lastname: Salmon
authors.forename: A
authors.initials: A
authors.lastname: Fischer
authors.forename: A
authors.initials: A
authors.lastname: Durandy
authors.forename: J L
authors.initials: JL
authors.lastname: Casanova
authors.forename: D S
authors.initials: DS
authors.lastname: Kumararatne
mesh_terms: D001500:BCG Vaccine / Q000276:immunology*; D001424:Bacterial Infections / Q000235:genetics*; D001483:Base Sequence; D002648:Child; D005260:Female; D005816:Genetic Complementation Test; D006099:Granuloma / Q000473:pathology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000172:deficiency / Q000235:genetics*; D007962:Leukocytes; D008198:Lymph Nodes / Q000473:pathology; D008969:Molecular Sequence Data; D009161:Mycobacterium / Q000276:immunology / Q000472:pathogenicity; D010375:Pedigree; D012477:Salmonella enteritidis / Q000276:immunology / Q000472:pathogenicity*; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion / Q000235:genetics; D014162:Transfection / Q000235:genetics
chemical_list: D001500:BCG Vaccine; D018664:Interleukin-12; D007371:Interferon-gamma