A novel antibody surrogate biomarker to monitor parasite persistence in Trypanosoma cruzi-infected patients

作者:Zrein Maan*; Granjon Elodie; Gueyffier Lucie; Caillaudeau Julie; Liehl Peter; Pottel Hans; Cardoso Clareci Silva; Oliveira Claudia Di Lorenzo; de Oliveira Lea Campos; Lee Tzong Hae; Ferreira Ariela Mota; Ribeiro Antonio Luiz P; Busch Michael P; Sabino Ester Cerdeira
来源:PLoS Neglected Tropical Diseases, 2018, 12(2): e0006226.
DOI:10.1371/journal.pntd.0006226

摘要

Background
Trypanosome cruzi parasite, the causative agent of Chagas disease, infects about six million individuals in more than 20 countries. Monitoring parasite persistence in infected individuals is of utmost importance to develop and evaluate treatments to control the disease. Routine screening for infected human individuals is achieved by serological assays; PCR testing to monitor spontaneous or therapy-induced parasitological cure has limitations due to the low and fluctuating parasitic load in circulating blood. The aim of the present study is to evaluate a newly developed antibody profiling assay as an indirect method to assess parasite persistence based on waning of antibodies following spontaneous or therapy-induced clearance of the infection.
Methodology/Principal findings
We designed a multiplex serology assay, an array of fifteen optimized T. cruziantigens, to evaluate antibody diversity in 1654 serum samples from chronic Chagas patients. One specific antibody response (antibody 3, Ab3) showed a strong correlation with T. cruzi parasite persistence as determined by T. cruzi PCR positive results. High and sustained Ab3 signal was strongly associated with PCR positivity in untreated patients, whereas significant decline in Ab3 signals was observed in BZN-treated patients who cleared parasitemia based on blood PCR results.
Conclusion/Significance
Ab3 is a new surrogate biomarker that strongly correlates with parasite persistence in chronic and benznidazole-treated Chagas patients. We hypothesize that Ab3 is induced and maintained by incessant stimulation of the immune system by tissue-based and shed parasites that are not consistently detectable by blood based PCR techniques. Hence, a simple immunoassay measurement of Ab3 could be beneficial for monitoring the infectious status of seropositive patients.