title: Inherited and acquired immunodeficiencies underlying tuberculosis in childhood.
abstract: Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb) and a few related mycobacteria, is a devastating disease, killing more than a million individuals per year worldwide. However, its pathogenesis remains largely elusive, as only a small proportion of infected individuals develop clinical disease either during primary infection or during reactivation from latency or secondary infection. Subacute, hematogenous, and extrapulmonary disease tends to be more frequent in infants, children, and teenagers than in adults. Life-threatening primary TB of childhood can result from known acquired or inherited immunodeficiencies, although the vast majority of cases remain unexplained. We review here the conditions conferring a predisposition to childhood clinical diseases caused by mycobacteria, including not only M.tb but also weakly virulent mycobacteria, such as BCG vaccines and environmental mycobacteria. Infections with weakly virulent mycobacteria are much rarer than TB, but the inherited and acquired immunodeficiencies underlying these infections are much better known. Their study has also provided genetic and immunological insights into childhood TB, as illustrated by the discovery of single-gene inborn errors of IFN-γ immunity underlying severe cases of TB. Novel findings are expected from ongoing and future human genetic studies of childhood TB in countries that combine a high proportion of consanguineous marriages, a high incidence of TB, and an excellent clinical care, such as Iran, Morocco, and Turkey.
authors.affiliation: St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale, INSERM-U1163, Paris, France; Paris Descartes University, Imagine Institute, Paris, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Boisson-Dupuis
authors.forename: Jacinta
authors.initials: J
authors.lastname: Bustamante
authors.forename: Jamila
authors.initials: J
authors.lastname: El-Baghdadi
authors.forename: Yildiz
authors.initials: Y
authors.lastname: Camcioglu
authors.forename: Nima
authors.initials: N
authors.lastname: Parvaneh
authors.forename: Safaa
authors.initials: S
authors.lastname: El Azbaoui
authors.forename: Aomar
authors.initials: A
authors.lastname: Agader
authors.forename: Amal
authors.initials: A
authors.lastname: Hassani
authors.forename: Naima
authors.initials: N
authors.lastname: El Hafidi
authors.forename: Nidal Alaoui
authors.initials: NA
authors.lastname: Mrani
authors.forename: Zineb
authors.initials: Z
authors.lastname: Jouhadi
authors.forename: Fatima
authors.initials: F
authors.lastname: Ailal
authors.forename: Jilali
authors.initials: J
authors.lastname: Najib
authors.forename: Ismail
authors.initials: I
authors.lastname: Reisli
authors.forename: Adil
authors.initials: A
authors.lastname: Zamani
authors.forename: Sebnem
authors.initials: S
authors.lastname: Yosunkaya
authors.forename: Saniye
authors.initials: S
authors.lastname: Gulle-Girit
authors.forename: Alisan
authors.initials: A
authors.lastname: Yildiran
authors.forename: Funda Erol
authors.initials: FE
authors.lastname: Cipe
authors.forename: Selda Hancerli
authors.initials: SH
authors.lastname: Torun
authors.forename: Ayse
authors.initials: A
authors.lastname: Metin
authors.forename: Basak Yildiz
authors.initials: BY
authors.lastname: Atikan
authors.forename: Nevin
authors.initials: N
authors.lastname: Hatipoglu
authors.forename: Cigdem
authors.initials: C
authors.lastname: Aydogmus
authors.forename: Sara Sebnem
authors.initials: SS
authors.lastname: Kilic
authors.forename: Figen
authors.initials: F
authors.lastname: Dogu
authors.forename: Neslihan
authors.initials: N
authors.lastname: Karaca
authors.forename: Guzide
authors.initials: G
authors.lastname: Aksu
authors.forename: Necil
authors.initials: N
authors.lastname: Kutukculer
authors.forename: Melike
authors.initials: M
authors.lastname: Keser-Emiroglu
authors.forename: Ayper
authors.initials: A
authors.lastname: Somer
authors.forename: Gonul
authors.initials: G
authors.lastname: Tanir
authors.forename: Caner
authors.initials: C
authors.lastname: Aytekin
authors.forename: Parisa
authors.initials: P
authors.lastname: Adimi
authors.forename: Seyed Alireza
authors.initials: SA
authors.lastname: Mahdaviani
authors.forename: Setareh
authors.initials: S
authors.lastname: Mamishi
authors.forename: Aziz
authors.initials: A
authors.lastname: Bousfiha
authors.forename: Ozden
authors.initials: O
authors.lastname: Sanal
authors.forename: Davood
authors.initials: D
authors.lastname: Mansouri
authors.forename: Jean-Laurent
authors.initials: JL
authors.lastname: Casanova
authors.forename: Laurent
authors.initials: L
authors.lastname: Abel
mesh_terms: D000367:Age Factors; D002648:Child; D004198:Disease Susceptibility / Q000276:immunology*; D005799:Genes, Dominant; D005808:Genes, Recessive; D020022:Genetic Predisposition to Disease; D006801:Humans; D016867:Immunocompromised Host; D007153:Immunologic Deficiency Syndromes / Q000150:complications* / Q000175:diagnosis / Q000209:etiology*; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D014376:Tuberculosis / Q000209:etiology*
keywords: IFN-γ; Mendelian susceptibility to mycobacterial diseases (MSMD); children; human genetics; primary immunodeficiency