New prognostic markers in Chagas disease by the use of nanoscopy

• Grant number: 09/14484-4
• Support Opportunities: Regular Research Grants
• Duration: May 01, 2010 - October 31, 2012
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal Investigator: Maria de Lourdes Higuchi
• Grantee: Maria de Lourdes Higuchi
• Host Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Chronic chagasic cardiopathy (CC) occurs in around 30% of the Trypanosoma cruzi infected individuals and is associated with lymphocytic myocarditis that is accompanied by C5b-9 complement deposition. The scarce amount of T. cruzi antigens does not explain the inflammation severity, and an autoimmune mechanism is suggested to involved. We hypothesized that association with microbial components from Archaea, Mycoplasma and Chlamydia might be associated with T. cruzi virulence as: a) archaeal proteolytic enzyme and archaeal genes were found in T. cruzi. b) T. cruzi mucins induced an intense inflammatory response similar of mycoplasmal lipopeptide and c) chlamydiae specific proteins were described in T.cruzi. In a preliminary study, we revised endomyocardial biopsies (EMBs) from 5 patients in Indeterminate form and 5 with CC through in situ hybridization and immuno electron microscopy and found correlations among components from Mycoplasma pneumoniae (MP), Chlamydia pneumoniae(CP), electron lucent archaeal-like bodies and Complement C5b-9 in CC group.The present project has the objective of verifying if there are associations between components from MP, CP and archaea, and T.cruzi, with the severity of Chagas disease through quantitative analysis of infectious elements, inflammatory infiltrate, fibrosis, C5b-9, apoptosis and cytokines, clinical abnormalities and survival time. A second objective is to verify if the analysis of infeccious particles in the serum may be a prognostic biomarker. Three studies will be made: a) Revision of EMBs performed at InCor from chagasic patients in different clinical forms. b) Analysis of nanoparticles present in the serum and in EMBs from CC patients in heart transplantation waiting-list. c) Analysis of nanoparticles in the serum of chagasic patients in different clinical forms. (AU)

Publicações científicas

(Referências obtidas automaticamente do Web of Science e do SciELO, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores)

HIGUCHI, MARIA DE LOURDES; KAWAKAMI, JOYCE T.; IKEGAMI, RENATA N.; REIS, MARCIA M.; PEREIRA, JAQUELINE DE JESUS; IANNI, BARBARA M.; BUCK, PAULA; DA SILVA OLIVEIRA, LUANDA MARA; SANTOS, MARILIA H. H.; HAJJAR, LUDHMILA A.; et al. Archaea Symbiont of T. cruzi Infection May Explain Heart Failure in Chagas Disease. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 8, NOV 21 2018. (09/14484-4)