Investigation of Urinary Peptides in Congenitally Infected Chagas Disease Patients
Abstract
Chagas disease (CD), caused by the protozoan Trypanosoma cruzi, is mainly transmitted through vectors, blood transfusions or from mothers to their infants. It is estimated that around 25% of new CD infections occur through congenital transmission. In most CD cases, the infection remains asymptomatic for years; however, in an estimated 20-30% of untreated patients, it can cause severe cardiac or gastrointestinal complications, or even death. Detecting and treating CD in the asymptomatic phase is critical as it allows for more efficient treatment before tissue damage progresses to an irreversible stage. CD is endemic in parts of Latin America and due to immigration, it's been growing to be a global public health concern. Current tests use blood specimens for diagnostics; most lack sensitivity and a combination of two independent tests is required. Our study presents a novel non-invasive nanoparticle-enhanced mass spectrometry method to detect T. cruzi peptides in the urine of infants with Chagas disease. Nanoparticles harvest and concentrate low abundance protein markers, preventing their degradation while excluding high molecular weight, abundant proteins. 193 T. cruzi derived peptides were identified in 15 congenitally infected Chagas infants living in endemic areas. Of the identified peptides, mucin-associated surface protein, trans-sialidase and dispersed gene family protein 1 (DGF-1) were highly represented in the urinary peptidome of Chagas patients. Members of those family groups are involved in host invasion and pathogenesis. In this study, we demonstrate for the first time that the nanoparticle-enhanced mass spectrometry test is able to detect urinary T. cruzi peptides in patients with Chagas disease. Few of those peptides were validated using two orthogonal technologies: Parallel reaction monitoring and Western Blot. Introducing a low cost and non-invasive test can be valuable for universal screening of Chagas disease for immigrants and for increasing endemic areas diagnostic testing.
Description
This thesis has been embargoed for 5 years and will not be available until July 2026 at the earliest.
Keywords
Mass spectrometry, Chagas Disease, Nanoparticles, Proteins, Diagnostics, Proteomics