We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Anti-Trypanosoma cruzi antibody profiling in patients with Chagas disease treated with benznidazole assessed by genome phage display.
- Authors
Rodriguez Carnero, Luis Antonio; Kuramoto, Andréia; Campos de Oliveira, Léa; Monteiro, Jhonatas Sirino; Setubal, João Carlos; Cunha-Neto, Edécio; Cerdeira Sabino, Ester; Giordano, Ricardo José
- Abstract
Background: There have been significant improvements in Chagas disease therapy and it is now widely accepted that most patients with chronic disease might benefit from therapy. However, there are challenges to monitor drug efficacy and cure for these patients, which are important impediments for current and future therapies. Trypanosoma cruzi-PCR is highly variable while IgG seroconversion takes decades yielding variable results depending on the antigen(s) used for the assay. Methods and results: We used the genomic phage display (gPhage) platform to perform a pairwise comparison of antigens and epitopes recognized by twenty individual patients with chronic Chagas disease before and after treatment with benznidazole. In total, we mapped 54,473 T. cruzi epitopes recognized by IgG from individual patients (N = 20) before benznidazole treatment. After treatment, the number of epitopes recognized by all patients was significantly smaller (21,254), a reduction consistent with a decrease in anti-T. cruzi antibodies. Most of these epitopes represent distinct fragments from the same protein and could, therefore, be grouped into 80 clusters of antigens. After three years of treatment with benznidazole, we observed a 64% reduction in the number of clusters of antigens recognized by patients (59 clusters before versus 21 clusters after treatment). The most abundant antigenic clusters recognized by patients correspond to the surface antigen CA-2 (B13) followed by the microtubule associated antigen, which highlights the value of these epitopes in Chagas disease diagnosis. Most importantly, quantitative pairwise comparison of gPhage data allowed for the prediction of patient response to treatment based on PCR status. Principal finding: Here, we compiled a list of antigens and epitopes preferentially recognized by Chagas disease patients before and after benznidazole treatment. Next, we observed that gPhage data correlated with patient PCR-status and could, therefore, predict patient response to treatment. Moreover, gPhage results suggest that overall, independent of PCR status, treatment led to a reduction in the presence of T. cruzi-specific antibody levels and the number of antigens and epitopes recognized by these patients. Conclusion: The gPhage platform use of unbiased library of antigens, which is different from conventional serological assays that rely on predetermined antigens, is a contribution for the development of novel diagnostic tools for Chagas disease. Author summary: Chagas disease, caused by the single-celled parasite Trypanosoma cruzi, can be a life-treating and debilitating illness. Because there is no vaccine and currently the only two available drugs are most effective if used during the early acute stage of the disease, treatment options for infected individuals are limited. Most individuals will only find out they have Chagas disease during a routine medical examination or in blood bank while donating blood, in which cases, they are already chronically infected. At this stage, treatment will not undo clinical mani-festations (i.e., cardiomyopathy) but may eliminate the parasite and prevent disease progression. Currently, polymerase chain reaction (PCR) and serological assays are the only diagnostic tools available, both with limi-tations in sensitivity and accuracy. The lack of effective molecular markers thus prevents physicians to deter-mine whether a patient is parasite free and cured from the disease. It also has important implications for the development of new drugs to treat Chagas disease. Here, we studied the reactivity of anti-T. cruzi antibodies in sera from a cohort of 20 patients that underwent treatment for Chagas disease using a new method developed by our group named gPhage. Using gPhage, we scanned all T. cruzi proteins to identify those that were reactive with the antibodies from each individual patient before and after treatment. In sum, gPhage data correlated with patient PCR-status and could, therefore, predict patient response to treatment. It also revealed a new set of T. cruzi proteins that could be useful for the development of future diagnostic methods.
- Subjects
CHAGAS' disease; CELL surface antigens; IMMUNOGLOBULINS; POLYMERASE chain reaction; DRUG efficacy
- Publication
PLoS Neglected Tropical Diseases, 2023, Vol 16, Issue 1, p1
- ISSN
1935-2727
- Publication type
Article
- DOI
10.1371/journal.pntd.0011019