Inherited and acquired immunodeficiencies underlying tuberculosis in childhood

St
ephanie Boisson-Dupuis, Jacinta Bustamante, Jamila El-Baghdadi, Yildiz Camcioglu, Nima Parvaneh, Safaa El Azbaoui, Aomar Agader, Amal Hassani, Naima El Hafidi, Nidal Alaoui Mrani, Zineb Jouhadi, Fatima Ailal, Jilali Najib, Ismail Reisli, Adil Zamani, Sebnem Yosunkaya, Saniye Gulle-Girit, Alisan Yildiran, Funda Erol Cipe, Selda Hancerli Torun, Ayse Metin, Basak Yildiz Atikan, Nevin Hatipoglu, Cigdem Aydogmus, Sara Sebnem Kilic, Figen Dogu, Neslihan Karaca, Guzide Aksu, Necil Kutukculer, Melike Keser-Emiroglu, Ayper Somer, Gonul Tanir, Caner Aytekin, Parisa Adimi, Seyed Alireza Mahdaviani, Setareh Mamishi, Aziz Bousfiha, Ozden Sanal, Davood Mansouri, Jean-Laurent Casanova, Laurent Abel

Pediatric Respiratory Diseases Research Centre, NRITLD, Masih Daneshvari Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran

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-c 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.
Keywords: primary immunodeficiency, human genetics, IFN-c, children, Mendelian susceptibility to mycobacterial diseases (MSMD)

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Immunological Reviews 264/2015