Laboratory of Emerging Pathogens, Division of Emerging and Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA.
Grupo Integrado de Pesquisas Em Biomarcadores, Instituto René Rachou, Fiocruz-Minas, Belo Horizonte, Brazil.
Sci Rep. 2020 Nov 11;10(1):19591. doi: 10.1038/s41598-020-76508-1.
Chagas drug discovery has been hampered by a lack of validated assays to establish treatment efficacy in pre-clinical animal models and in patients infected with T. cruzi. Reduced levels of parasite secreted antigens in the blood of infected hosts could be used to demonstrate treatment efficacy. A published proteomic study of parasite secreted antigens identified the hypothetical protein Tc_5171 as a secreted antigen. In this report, we developed Tc_5171 specific antibodies and showed that the native protein was expressed by the three life cycle stages of the parasite. Anti-peptide antibodies were able to detect the parasite antigen in blood of infected mice during the acute and the chronic phase of infection. Benznidazole treatment of infected mice significantly reduced their blood antigen levels. Of clinical significance, patients diagnosed with Chagas disease, either asymptomatic or with cardiac clinical symptoms had significantly higher Tc_5171 antigen levels compared to endemic controls. Pair-wise analysis, before and after Benznidazole treatment, of patients with asymptomatic Chagas disease showed a significant reduction in antigen levels post treatment. Taken together, our results indicate that Tc_5171 could be used as a novel biomarker of Chagas disease for diagnosis and to assess treatment efficacy.
克氏锥虫病的药物发现一直受到缺乏验证的检测方法的阻碍，这些方法无法在临床前动物模型和感染 T. cruzi 的患者中确立治疗效果。减少感染宿主血液中寄生虫分泌的抗原水平可以用来证明治疗效果。已发表的寄生虫分泌抗原的蛋白质组学研究将假设蛋白 Tc_5171 鉴定为分泌抗原。在本报告中，我们开发了 Tc_5171 特异性抗体，并表明天然蛋白在寄生虫的三个生命周期阶段均有表达。抗肽抗体能够在感染急性和慢性阶段的感染小鼠的血液中检测到寄生虫抗原。贝那唑嗪治疗感染小鼠可显著降低其血液抗原水平。具有临床意义的是，与地方流行对照组相比，诊断为恰加斯病的患者，无论是无症状还是有心脏临床症状，其 Tc_5171 抗原水平均显著升高。对无症状恰加斯病患者进行贝那唑嗪治疗前后的两两分析表明，治疗后抗原水平显著降低。总之，我们的结果表明，Tc_5171 可作为一种新的恰加斯病生物标志物，用于诊断和评估治疗效果。
