Department of Infection and Digestion, Children's Hospital of Chongqing Medical University, No. 136 Zhongshan Er Road, Yuzhong District, Chongqing 400014, PR China.
Tuberculosis (Edinb). 2011 Jul;91(4):287-92. doi: 10.1016/j.tube.2011.05.001. Epub 2011 Jun 12.
In vitro and in animal studies have suggested an important role for the Mycobacterium tuberculosis PE_PGRS33 protein in the pathogenesis of TB. A significant level of PE_PGRS33 gene DNA polymorphism among clinical isolates from adult tuberculosis (TB) patients and its association with clinical and epidemiological phenotypes of the disease has been found. To better understand the role of PE_PGRS33 protein in the pathogenesis pediatric TB, we investigated DNA polymorphism of the PE_PGRS33 gene among 101 of pediatric TB patients' isolates and assessed the relationship between the PE_PGRS33 sequence variation and clinical characteristics of TB. Twelve different PE_PGRS33 sequence variations representing 12 different alleles were observed among the 101 M. tuberculosis clinical isolates investigated. Of these 101 isolates, 62(59.41%) had PE_PGRS33 alleles that would result in a change in the amino acid sequence of the PE_PGRS33 protein. The degree of DNA polymorphism within individual M. tuberculosis isolates from pediatric TB patients was remarkably lower than that previously found in M. tuberculosis isolates from adults TB patients. The frequency distribution of isolates having PE_PGRS33 gene sequence variations was similar between Beijing and non-Beijing families of the pathogen. Patients having TB meningitis and negative PPD skin test results appeared to be more likely to be infected by isolates having a mutant type of the PE_PGRS33 gene than patients who had no TB meningitis (OR 2.54, 95% CI [1.11-5.84]) and patients who had positive PPD-skin test results (OR 4.26, 95% CI [1.14-12.86]), respectively. This study provides new insight into the molecular pathogenesis of pediatric TB.
在体外和动物研究中，结核分枝杆菌 PE_PGRS33 蛋白在结核病发病机制中发挥了重要作用。在成人结核病（TB）患者的临床分离株中发现了 PE_PGRS33 基因 DNA 多态性水平显著，并且与疾病的临床和流行病学表型相关。为了更好地了解 PE_PGRS33 蛋白在小儿结核病发病机制中的作用，我们调查了 101 例小儿结核病患者分离株中 PE_PGRS33 基因的 DNA 多态性，并评估了 PE_PGRS33 序列变异与结核病临床特征之间的关系。在所研究的 101 株结核分枝杆菌临床分离株中观察到 12 种不同的 PE_PGRS33 序列变异，代表 12 种不同的等位基因。在这 101 个分离株中，62 个（59.41%）具有导致 PE_PGRS33 蛋白氨基酸序列改变的 PE_PGRS33 等位基因。来自小儿结核病患者的结核分枝杆菌分离株个体内的 DNA 多态性程度明显低于以前在成人结核病患者的结核分枝杆菌分离株中发现的程度。北京家族和非北京家族的病原体的 PE_PGRS33 基因序列变异的分离株的频率分布相似。患有结核性脑膜炎和 PPD 皮肤试验结果阴性的患者似乎比没有结核性脑膜炎的患者（OR 2.54，95%CI [1.11-5.84]）和 PPD 皮肤试验阳性的患者（OR 4.26，95%CI [1.14-12.86]）更容易被具有突变型 PE_PGRS33 基因的分离株感染。这项研究为小儿结核病的分子发病机制提供了新的见解。
