Inborn errors of IL-12/23- and IFN-gamma-mediated immunity: molecular, cellular, and clinical features.
Mendelian susceptibility to mycobacterial diseases confers predisposition to clinical disease caused by weakly virulent mycobacterial species in otherwise healthy individuals. Since 1996, disease-causing mutations have been found in five autosomal genes (IFNGR1, IFNGR2, STAT1, IL12B, IL12BR1) and one X-linked gene (NEMO). These genes display a high degree of allelic heterogeneity, defining at least 13 disorders. Although genetically different, these conditions are immunologically related, as all result in impaired IL-12/23-IFN-gamma-mediated immunity. These disorders were initially thought to be rare, but have now been diagnosed in over 220 patients from over 43 countries worldwide. We review here the molecular, cellular, and clinical features of patients with inborn errors of the IL-12/23-IFN-gamma circuit.
Filipe-Santos
Orchidée
O
Laboratory of Human Genetics of Infectious Diseases, University of Paris René Descartes-INSERM U 550, Necker Medical School, 75015 Paris, France, EU.
Bustamante
Jacinta
J
Chapgier
Ariane
A
Vogt
Guillaume
G
de Beaucoudrey
Ludovic
L
Feinberg
Jacqueline
J
Jouanguy
Emmanuelle
E
Boisson-Dupuis
Stéphanie
S
Fieschi
Claire
C
Picard
Capucine
C
Casanova
Jean-Laurent
JL
D000818:Animals; D030342:Genetic Diseases, Inborn / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics* / Q000276:immunology; D018664:Interleukin-12 / Q000235:genetics* / Q000276:immunology; D053759:Interleukin-23 / Q000235:genetics* / Q000276:immunology; D009154:Mutation
D053759:Interleukin-23; D018664:Interleukin-12; D007371:Interferon-gamma