title: Mendelian susceptibility to mycobacterial disease: genetic, immunological, and clinical features of inborn errors of IFN-γ immunity.
abstract: Mendelian susceptibility to mycobacterial disease (MSMD) is a rare condition characterized by predisposition to clinical disease caused by weakly virulent mycobacteria, such as BCG vaccines and environmental mycobacteria, in otherwise healthy individuals with no overt abnormalities in routine hematological and immunological tests. MSMD designation does not recapitulate all the clinical features, as patients are also prone to salmonellosis, candidiasis and tuberculosis, and more rarely to infections with other intramacrophagic bacteria, fungi, or parasites, and even, perhaps, a few viruses. Since 1996, nine MSMD-causing genes, including seven autosomal (IFNGR1, IFNGR2, STAT1, IL12B, IL12RB1, ISG15, and IRF8) and two X-linked (NEMO, and CYBB) genes have been discovered. The high level of allelic heterogeneity has already led to the definition of 18 different disorders. The nine gene products are physiologically related, as all are involved in IFN-γ-dependent immunity. These disorders impair the production of (IL12B, IL12RB1, IRF8, ISG15, NEMO) or the response to (IFNGR1, IFNGR2, STAT1, IRF8, CYBB) IFN-γ. These defects account for only about half the known MSMD cases. Patients with MSMD-causing genetic defects may display other infectious diseases, or even remain asymptomatic. Most of these inborn errors do not show complete clinical penetrance for the case-definition phenotype of MSMD. We review here the genetic, immunological, and clinical features of patients with inborn errors of IFN-γ-dependent immunity.
authors.affiliation: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale, INSERM-U1163, Paris, France, EU; Paris Descartes University, Imagine Institute, Paris, France, EU; Center for the Study of Primary Immunodeficiencies, Assistance Publique-Hôpitaux de Paris AP-HP, Necker-Enfants Malades Hospital, Paris, France, EU. Electronic address: jacinta.bustamante@inserm.fr.
authors.forename: Jacinta
authors.initials: J
authors.lastname: Bustamante
authors.affiliation: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale, INSERM-U1163, Paris, France, EU; Paris Descartes University, Imagine Institute, Paris, France, EU; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Boisson-Dupuis
authors.affiliation: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale, INSERM-U1163, Paris, France, EU; Paris Descartes University, Imagine Institute, Paris, France, EU; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.
authors.forename: Laurent
authors.initials: L
authors.lastname: Abel
authors.affiliation: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale, INSERM-U1163, Paris, France, EU; Paris Descartes University, Imagine Institute, Paris, France, EU; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA; Howard Hughes Medical Institute, NY, USA; Pediatric Hematology-Immunology Unit, Necker Hospital for Sick Children, Paris, France, EU.
authors.forename: Jean-Laurent
authors.initials: JL
authors.lastname: Casanova
mesh_terms: D002177:Candidiasis / Q000235:genetics / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D060085:Coinfection; D018740:Genetic Heterogeneity; D020022:Genetic Predisposition to Disease; D005838:Genotype; D054884:Host-Pathogen Interactions / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D007371:Interferon-gamma / Q000235:genetics* / Q000276:immunology; D008661:Metabolism, Inborn Errors / Q000235:genetics* / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D010641:Phenotype; D012480:Salmonella Infections / Q000235:genetics / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D012720:Severity of Illness Index; D014397:Tuberculosis, Pulmonary / Q000235:genetics* / Q000276:immunology / Q000382:microbiology / Q000473:pathology
chemical_list: D007371:Interferon-gamma
keywords: BCG; IFN-γ; IL-12; ISG15; Mycobacteriosis; Primary immunodeficiency; Tuberculosis