IL-12Rβ1 deficiency in two of fifty children with severe tuberculosis from Iran, Morocco, and Turkey.

• Main Authors: Stéphanie Boisson-Dupuis, Jamila El Baghdadi, Nima Parvaneh, Aziz Bousfiha, Jacinta Bustamante, Jacqueline Feinberg, Arina Samarina, Audrey V Grant, Lucile Janniere, Naima El Hafidi, Amal Hassani, Daniel Nolan, Jilali Najib, Yildiz Camcioglu, Nevin Hatipoglu, Cigdem Aydogmus, Gonul Tanir, Caner Aytekin, Melike Keser, Ayper Somer, Guside Aksu, Necil Kutukculer, Davood Mansouri, Alireza Mahdaviani, Setareh Mamishi, Alexandre Alcais, Laurent Abel, Jean-Laurent Casanova
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2011-04-01
• Series: PLoS ONE
• Online Access: http://europepmc.org/articles/PMC3076373?pdf=render

In the last decade, autosomal recessive IL-12Rβ1 deficiency has been diagnosed in four children with severe tuberculosis from three unrelated families from Morocco, Spain, and Turkey, providing proof-of-principle that tuberculosis in otherwise healthy children may result from single-gene inborn errors of immunity. We aimed to estimate the fraction of children developing severe tuberculosis due to IL-12Rβ1 deficiency in areas endemic for tuberculosis and where parental consanguinity is common.We searched for IL12RB1 mutations in a series of 50 children from Iran, Morocco, and Turkey. All children had established severe pulmonary and/or disseminated tuberculosis requiring hospitalization and were otherwise normally resistant to weakly virulent BCG vaccines and environmental mycobacteria. In one child from Iran and another from Morocco, homozygosity for loss-of-function IL12RB1 alleles was documented, resulting in complete IL-12Rβ1 deficiency. Despite the small sample studied, our findings suggest that IL-12Rβ1 deficiency is not a very rare cause of pediatric tuberculosis in these countries, where it should be considered in selected children with severe disease.This finding may have important medical implications, as recombinant IFN-γ is an effective treatment for mycobacterial infections in IL-12Rβ1-deficient patients. It also provides additional support for the view that severe tuberculosis in childhood may result from a collection of single-gene inborn errors of immunity.