IL-12Rβ1 Deficiency in Two of Fifty Children with Severe Tuberculosis from Iran, Morocco, and Turkey
IL-12Rβ1 Deficiency in Two of Fifty Children with Severe Tuberculosis from Iran, Morocco, and Turkey
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DOI：
10.1371/journal.pone.0018524
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发表时间：
2011-04-13
期刊：
影响因子：
3.7
通讯作者：
Casanova, Jean-Laurent
中科院分区：
文献类型：
--
作者：
Boisson-Dupuis, Stephanie;El Baghdadi, Jamila;Casanova, Jean-Laurent
背景与目的：在过去的十年中，来自摩洛哥、西班牙和土耳其的三个不相关家庭的四名患有严重结核病的儿童被诊断为常染色体隐性IL-12 R β 11缺乏症，这提供了原则证明，即在其他方面健康的儿童中，结核病可能是由单基因先天性免疫缺陷引起的。我们的目的是估计部分儿童发展严重的结核病由于IL-12 R β 1缺乏症在结核病流行的地区，父母的血缘关系是常见的。方法和主要发现：我们寻找了一系列的50名儿童从伊朗，摩洛哥，土耳其的IL-12 RB 1突变。所有儿童都患有需要住院治疗的严重肺结核和/或播散性结核，并且通常对弱毒力卡介苗和环境分枝杆菌具有耐药性。在来自伊朗的一名儿童和来自摩洛哥的另一名儿童中，记录了功能丧失的IL-12 RB 1等位基因的纯合性，导致完全的IL-12 R β 1缺乏。尽管小样本研究，我们的研究结果表明，IL-12 R β 1缺乏症是不是一个非常罕见的原因，在这些国家，它应该被认为是在选定的儿童严重diseases.Significance：这一发现可能具有重要的医学意义，作为重组IFN-γ是一种有效的治疗分枝杆菌感染的IL-12 R β 1缺乏症患者。它还提供了额外的支持，认为严重的结核病在儿童可能会导致一系列单基因先天性免疫缺陷。
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.