PDF(Pubmed)
Abstract：
UNASSIGNED: Chagas disease, caused by the Trypanosoma cruzi parasite infection, is a potentially life-threatening neglected tropical disease with a worldwide distribution. During the chronic phase of the disease, there exists a fragile balance between the host immune response and parasite replication that keeps patients in a clinically-silent asymptomatic stage for years or even decades. However, in 40% of patients, the disease progresses to clinical manifestations mainly affecting and compromising the cardiac system. Treatment is recommended in the chronic phase, although there are no early markers of its effectiveness. The aim of this study is to identify differential expression changes in genes involved in the immune response in antigen-restimulated PBMC from chronic patients with Chagas disease due to benznidazole treatment.
UNASSIGNED: Thus, high-throughput real-time qPCR analysis has been performed to simultaneously determine global changes in the expression of 106 genes involved in the immune response in asymptomatic (IND) and early cardiac manifestations (CCC I) Chagas disease patients pre- and post-treatment with benznidazole.
UNASSIGNED: The results revealed that 7 out of the 106 analyzed genes were differentially expressed (4 up- and 3 downregulated) after treatment in IND patients and 15 out of 106 (3 up- and 12 downregulated) after treatment of early cardiac Chagas disease patients. Particularly in CCC I patients, regulation of the expression level of some of these genes towards a level similar to that of healthy subjects suggests a beneficial effect of treatment and supports recommendation of benznidazole administration to early cardiac Chagas disease patients. The data obtained also demonstrated that both in asymptomatic patients and in early cardiac chronic patients, after treatment with benznidazole there is a negative regulation of the proinflammatory and cytotoxic responses triggered as a consequence of T. cruzi infection and the persistence of the parasite. This downregulation of the immune response likely prevents marked tissue damage and healing in early cardiac patients, suggesting its positive effect in controlling the pathology.
UNASSIGNED: Thus, high-throughput real-time qPCR analysis has been performed to simultaneously determine global changes in the expression of 106 genes involved in the immune response in asymptomatic (IND) and early cardiac manifestations (CCC I) Chagas disease patients pre- and post-treatment with benznidazole.
UNASSIGNED: The results revealed that 7 out of the 106 analyzed genes were differentially expressed (4 up- and 3 downregulated) after treatment in IND patients and 15 out of 106 (3 up- and 12 downregulated) after treatment of early cardiac Chagas disease patients. Particularly in CCC I patients, regulation of the expression level of some of these genes towards a level similar to that of healthy subjects suggests a beneficial effect of treatment and supports recommendation of benznidazole administration to early cardiac Chagas disease patients. The data obtained also demonstrated that both in asymptomatic patients and in early cardiac chronic patients, after treatment with benznidazole there is a negative regulation of the proinflammatory and cytotoxic responses triggered as a consequence of T. cruzi infection and the persistence of the parasite. This downregulation of the immune response likely prevents marked tissue damage and healing in early cardiac patients, suggesting its positive effect in controlling the pathology.
摘要：
■查加斯病，由克氏锥虫寄生虫感染引起的，是一种可能危及生命的被忽视的热带病，分布在世界各地。在疾病的慢性阶段，宿主免疫反应和寄生虫复制之间存在一种脆弱的平衡,使患者在临床上处于无症状阶段数年甚至数十年.然而,40%的病人,该疾病发展为主要影响和损害心脏系统的临床表现。建议在慢性期进行治疗，尽管没有早期的有效性标记。这项研究的目的是鉴定由于苯并咪唑治疗而导致的查加斯病慢性患者的抗原再刺激的PBMC中参与免疫反应的基因的差异表达变化。
■因此，已进行了高通量实时qPCR分析，以同时确定无症状（IND）和早期心脏表现（CCCI）Chagas病患者治疗前后的106个与免疫反应有关的基因表达的整体变化。苯并硝唑。
■结果显示，在IND患者治疗后，106个分析基因中有7个差异表达（4个上调和3个下调），在早期心脏病患者治疗后，106个基因中有15个差异表达（3个上调和12个下调）。特别是在CCCI患者中，将其中一些基因的表达水平调节至与健康受试者相似的水平，表明治疗的有益效果，并支持对早期心脏Chagas病患者推荐使用苯并硝唑。获得的数据还表明，在无症状患者和早期心脏病患者中，在用苯并硝唑治疗后,由于克氏锥虫感染和寄生虫的持续存在而引发的促炎和细胞毒性反应的负调节。这种免疫反应的下调可能阻止早期心脏病患者明显的组织损伤和愈合。表明其在控制病理方面的积极作用。
■因此，已进行了高通量实时qPCR分析，以同时确定无症状（IND）和早期心脏表现（CCCI）Chagas病患者治疗前后的106个与免疫反应有关的基因表达的整体变化。苯并硝唑。
■结果显示，在IND患者治疗后，106个分析基因中有7个差异表达（4个上调和3个下调），在早期心脏病患者治疗后，106个基因中有15个差异表达（3个上调和12个下调）。特别是在CCCI患者中，将其中一些基因的表达水平调节至与健康受试者相似的水平，表明治疗的有益效果，并支持对早期心脏Chagas病患者推荐使用苯并硝唑。获得的数据还表明，在无症状患者和早期心脏病患者中，在用苯并硝唑治疗后,由于克氏锥虫感染和寄生虫的持续存在而引发的促炎和细胞毒性反应的负调节。这种免疫反应的下调可能阻止早期心脏病患者明显的组织损伤和愈合。表明其在控制病理方面的积极作用。
