IL-12R beta 1 Deficiency in Two of Fifty Children with Severe Tuberculosis from Iran, Morocco, and Turkey
Küçük Resim Yok
Tarih
2011
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Public Library Science
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
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.
Açıklama
Anahtar Kelimeler
Kaynak
Plos One
WoS Q Değeri
Q1
Scopus Q Değeri
Cilt
6
Sayı
4
