期刊
PLOS ONE
卷 6, 期 4, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0018524
关键词
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资金
- Schlumberger Foundation
- BNP-Paribas Foundation
- Foundation for Medical Research (FRM)
- Institut Universitaire de France
- French National Agency for Research (ANR)
- EU [HEALTH-F3-2008-200732]
- Bill and Melinda Gates Foundation
- St. Giles Foundation
- Jeffrey Modell Foundation
- Talecris Biotherapeutics
- Rockefeller University Center for Clinical and Translational Science [5UL1RR024143]
- Rockefeller University
- National Institute of Allergy and Infectious Diseases [1U01AI088685]
Background and Objectives: In the last decade, autosomal recessive IL-12R beta 11 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-12R beta 1 deficiency in areas endemic for tuberculosis and where parental consanguinity is common. Methods and Principal Findings: 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-12R beta 1 deficiency. Despite the small sample studied, our findings suggest that IL-12R beta 1 deficiency is not a very rare cause of pediatric tuberculosis in these countries, where it should be considered in selected children with severe disease. Significance: This finding may have important medical implications, as recombinant IFN-gamma is an effective treatment for mycobacterial infections in IL-12R beta 1-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.
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