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Discovery of biomarkers of Chagas' disease in urine using mass spectrometry techniques

Grant number: 18/13283-4
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): November 01, 2018
Effective date (End): August 31, 2021
Field of knowledge:Biological Sciences - Biochemistry - Chemistry of Macromolecules
Principal researcher:Giuseppe Palmisano
Grantee:Gilberto Santos de Oliveira
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:14/06863-3 - Post-translational modifications in cancer and parasite infection diagnosis: methodological approaches and biological implications, AP.JP


Discovered and characterized in 1909 by Carlos Chagas, Trypanosoma cruzi is the etiologic agent of Chagas' disease. During the chronic phase of Chagas' disease, where parasitemia is low, the diagnosis is based on the search for antibodies against T. cruzi antigens in the blood. To increase the certainty of the result, is recommended two serological methods (usually ELISA, Indirect Immunofluorescence or Indirect Hemagglutination) for diagnostic confirmation. Although the aforementioned assays are widely used, none of them has sufficient specificity to define the diagnosis alone, especially in patients from regions where there is geographical overlap with other parasites, especially of the genus Leishmania or T. rangeli. An interesting alternative that was raised by some authors in the 1980s is the use of molecules of diagnostic interest (antibodies, antigens or immunomplexes) in the patients' urine. During the last years techniques of proteomics have been applied to many fields of Medicine. One of the applications is Nephrology for the better understanding of renal physiology, to explore the completeness of disease mechanisms and identify new biomarkers. Moreover, most of the proteins in the urine are glycosylated. Their properties are unique, making them an important source of biomarkers. In general, perceived that despite significant advances in diagnostic methods for the detection of T. cruzi infection, there are some gaps that need to be filled. The fact that conventional IgG antibody serology will remain positive over the life of the patient, despite the persistence of the humoral immune response, is a limitation, since it does not allow a reliable criterion of cure. On the other hand, the lack of a reliable system to follow the evolution of the treatment generates serious limitations to evaluate the performance of new treatment protocols with existing drugs or new drugs. Due to these limitations, we propose to develop new methods of diagnosis based on mass spectrometry for the detection of T. cruzi infection using urine as a source of biomarkers. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
COUTINHO, JOAO V. P.; ROSA-FERNANDES, LIVIA; MULE, SIMON NGAO; DE OLIVEIRA, GILBERTO SANTOS; MANCHOLA, NUBIA CAROLINA; SANTIAGO, VERONICA FEIJOLI; COLLI, WALTER; WRENGER, CARSTEN; MANSO ALVES, MARIA JULIA; PALMISANO, GIUSEPPE. The thermal proteome stability profile of Trypanosoma cruzi in epimastigote and trypomastigote life stages. JOURNAL OF PROTEOMICS, v. 248, SEP 30 2021. Web of Science Citations: 0.
MULE, SIMON NGAO; COSTA-MARTINS, ANDRE GUILHERME; ROSA-FERNANDES, LIVIA; DE OLIVEIRA, GILBERTO SANTOS; RODRIGUES, CARLA MONADELI F.; QUINA, DANIEL; ROSEIN, GRAZIELLA E.; GERALDES TEIXEIRA, MARTA MARIA; PALMISANO, GIUSEPPE. PhyloQuant approach provides insights into Trypanosoma cruzi evolution using a systems-wide mass spectrometry-based quantitative protein profile. COMMUNICATIONS BIOLOGY, v. 4, n. 1 MAR 11 2021. Web of Science Citations: 0.
MULE, S. N.; MANCHOLA, N. C.; DE OLIVEIRA, G. S.; PEREIRA, M.; MAGALHAES, R. D. M.; TEIXEIRA, A. A.; COLLI, W.; ALVES, M. J. M.; PALMISANO, G. Proteome-wide modulation of S-nitrosylation in Trypanosoma cruzi trypomastigotes upon interaction with the host extracellular matrix. JOURNAL OF PROTEOMICS, v. 231, JAN 16 2021. Web of Science Citations: 0.

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