title: Nontuberculous mycobacterial infections in children with inborn errors of the immune system.
abstract: Severe mycobacterial disease is mostly confined to patients who are immunocompromized either by acquired or inherited causes. One such genetic disorder is Mendelian Susceptibility to Mycobacterial Disease (MSMD), a hot topic within the field of primary immunodeficiency. This single gene disorder is characterized by isolated infection with mycobacteria or Salmonella due to a defect in the type-1 cytokine response. In the last two decades, ten genes have been labeled as causing MSMD when they harbor germline mutations, namely IL12B, IL12RB1, IFNGR1, IFNGR2, STAT1, IKBKG, CYBB, TYK2, IRF8 and ISG15. The mutations lead to either insufficient production of IFN-γ, or to an insufficient response to the cytokine. Current treatment options include recombinant IFN-γ and hematologic stem cell transplantation (HSCT). In the future, gene therapy, antisense-mediated exon skipping and chemical intervention in glycosylation problems may become successful alternatives. Furthermore, it is likely that many new candidate genes and pathways crucial for mycobacterial immunity will be identified.
authors.affiliation: Department of Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. Electronic address: m.h.haverkamp@lumc.nl.
authors.forename: Margje H
authors.initials: MH
authors.lastname: Haverkamp
authors.forename: Esther
authors.initials: E
authors.lastname: van de Vosse
authors.forename: Jaap T
authors.initials: JT
authors.lastname: van Dissel
mesh_terms: D002648:Child; D002675:Child, Preschool; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007371:Interferon-gamma / Q000627:therapeutic use; D009165:Mycobacterium Infections, Nontuberculous / Q000150:complications / Q000453:epidemiology* / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D009170:Nontuberculous Mycobacteria / Q000302:isolation & purification*; D012475:Salmonella / Q000302:isolation & purification; D012480:Salmonella Infections / Q000453:epidemiology / Q000235:genetics / Q000276:immunology / Q000628:therapy
chemical_list: D007371:Interferon-gamma
keywords: Children; MSMD; Mutation; Mycobacterial infection