IL-17A, a possible biomarker for the evaluation of treatment response in Trypanosoma cruzi infected children: A 12-months follow-up study in Bolivia
IL-17A, a possible biomarker for the evaluation of treatment response in Trypanosoma cruzi infected children: A 12-months follow-up study in Bolivia
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DOI：
10.1371/journal.pntd.0007715
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发表时间：
2019-09
影响因子：
3.8
通讯作者：
Clara Vásquez Velásquez;G. Russomando;Emilio E. Espínola;Z. Sánchez;Kota Mochizuki;Y. Roca;J. Revollo;Angélica Guzmán;B. Quiroga;Susana Rios Morgan;Roberto Vargas Ortiz;Alberto Zambrana Ortega;E. Espinoza;J. Nishizawa;M. G. Kamel;M. Kikuchi;Shusaku Mizukami;K. Na-Bangchang;Nguyen Tien Huy;K. Hirayama
中科院分区：
文献类型：
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作者：
Clara Vásquez Velásquez;G. Russomando;Emilio E. Espínola;Z. Sánchez;Kota Mochizuki;Y. Roca;J. Revollo;Angélica Guzmán;B. Quiroga;Susana Rios Morgan;Roberto Vargas Ortiz;Alberto Zambrana Ortega;E. Espinoza;J. Nishizawa;M. G. Kamel;M. Kikuchi;Shusaku Mizukami;K. Na-Bangchang;Nguyen Tien Huy;K. Hirayama
背景2006年玻利维亚实施了查加斯病国家计划，通过媒介控制大大减少了感染人数。随后，对居住在病媒控制区血清阳性的学龄儿童开始了苯硝唑(BNZ)的治疗方案。方法和结果：我们进行了为期12个月的随访研究，在治疗过程中和治疗后分别采集了7个血样。进行血清学、常规诊断聚合酶链式反应(CPCR)和实时荧光定量聚合酶链式反应(QPCR)。同时检测血浆Th1/Th2/Th17细胞因子水平。在103名血清阳性的儿童中，约有73人遵守了BNZ的规定，其中三次因副作用而中断。为了评估每个个体的治疗效果，观察了最后6个月随访期间的cPCR值和qPCR值。在57例完成随访的儿童中，6例(11%)同时有cPCR(+)和qPCR(+)(无反应)，24例(42%)cPCR(-)但有qPCR(+)(模棱两可)，27例(47%)cPCR(-)和qPCR(-)(反应)。在14种Th1/Th2/Th17细胞因子中，血清阳性组治疗前IL-17A水平显著高于年龄匹配的血清阴性组，治疗1年后IL-17A水平显著下降至正常水平。此外，在整个随访研究中，IL-17A水平与qPCR检测到的寄生虫数量呈正相关。在12个月的时间点，非反应性受试者的IL-17A水平显著高于反应性受试者或模棱两可的受试者，提示IL-17A可能有助于判断对BNZ治疗的反应性。结论血浆IL-17A水平可作为检测克氏毛滴虫持续感染及其慢性炎症的生物标志物。
Background The National Program for Chagas disease was implemented in Bolivia in 2006, and it greatly decreased the number of infections through vector control. Subsequently, a treatment regimen of benznidazole (BNZ) was started in seropositive school-age children living in certified vector control areas. Methods and findings We conducted a 12-month follow-up study and seven blood samples were taken during and after the treatment. Serology, conventional diagnostic PCR (cPCR) and quantitative Real-time PCR (qPCR) were performed. Plasma Th1/Th2/Th17 cytokines levels were also determined. Approximately 73 of 103 seropositive children complied with BNZ, with three interruptions due to side effects. To evaluate each individual’s treatment efficacy, the cPCR and qPCR values during the final 6 months of the follow-up period were observed. Among 57 children who completed follow-up, 6 individuals (11%) showed both cPCR(+) and qPCR(+) (non reactive), 24 (42%) cPCR(-) but qPCR(+) (ambiguous) and 27 (47%) cPCR(-) and qPCR(-) (reactive). Within 14 Th1/Th2/Th17 cytokines, IL-17A showed significantly higher levels in seropositive children before the treatment compared to age-matched seronegative children and significantly decreased to the normal level one-year after. Moreover, throughout the follow-up study, IL-17A levels were positively co-related to parasite counts detected by qPCR. At the 12 months’ time point, IL-17A levels of non-reactive subjects were significantly higher than either those of reactive or ambiguous subjects suggesting that IL-17A might be useful to determine the reactivity to BNZ treatment. Conclusions Plasma levels of IL-17A might be a bio-marker for detecting persistent infection of T. cruzi and its chronic inflammation.