Döffinger R, Altare F, Casanova J L
Laboratory of Human Genetics of Infectious Diseases, Necker Medical School, 156, rue de Vaugirard, 75015, Paris, France.
Microbes Infect. 2000 Nov;2(13):1553-7. doi: 10.1016/s1286-4579(00)01311-3.
Mendelian susceptibility to poorly virulent mycobacterial species, such as bacillus Calmette-Guérin (BCG) and environmental nontuberculous mycobacteria (NTM), is a phenotypically heterogeneous syndrome. It has therefore long been suspected to be genetically heterogeneous. In the past 5 years, this prediction has been confirmed and different types of mutations (dominant or recessive, nonfunctional or hypofunctional) in four genes (IFNGR1, IFNGR2, IL12B, IL12RB1) have revealed both allelic and nonallelic heterogeneity. The eight disorders resulting from these mutations are genetically different but immunologically related, as impaired IFN-gamma-mediated immunity is the common pathogenic mechanism accounting for mycobacterial infection in all patients. The severity of the phenotype depends on the genotype. Complete IFN-gammaR1 and IFN-gammaR2 deficiencies predispose patients to a more severe clinical course than partial IFN-gammaR1 and IFN-gammaR2 deficiencies and complete IL-12 p40 and IL-12Rbeta1 deficiencies.
对毒性较弱的分枝杆菌物种（如卡介苗（BCG）和环境非结核分枝杆菌（NTM））的孟德尔易感性是一种表型异质性综合征。因此，长期以来人们一直怀疑它在基因上也是异质性的。在过去5年中，这一预测得到了证实，四个基因（IFNGR1、IFNGR2、IL12B、IL12RB1）中的不同类型突变（显性或隐性、无功能或功能减退）揭示了等位基因和非等位基因的异质性。这些突变导致的八种疾病在基因上不同，但在免疫上相关，因为干扰素-γ介导的免疫受损是所有患者分枝杆菌感染的共同致病机制。表型的严重程度取决于基因型。完全缺乏干扰素-γR1和干扰素-γR2比部分缺乏干扰素-γR1和干扰素-γR2以及完全缺乏白细胞介素-12 p40和白细胞介素-12Rβ1更容易使患者出现更严重的临床病程。
