Beschreibung:
<jats:p>
Chagas cardiomyopathy (CC) is caused by the infection of
<jats:italic>Trypanosoma cruzi</jats:italic>
(
<jats:italic>T. cruzi</jats:italic>
) and represents a major etiology for heart failure in Latin America. Trying fill gaps related to humoral response in CC, we used a PhIP-Seq technology to describe differential IgG profile between individuals with CC and individuals infected by
<jats:italic>T. cruzi</jats:italic>
, but without symptoms (Indeterminate - IND). We built a library comprising all
<jats:italic>T. cruzi</jats:italic>
proteome (12766 proteins) and incubated against 1293 serum samples: 396
<jats:italic>T. cruzi</jats:italic>
<jats:underline>seronegative</jats:underline>
samples (98 controls and 298 individuals with cardiomyopathy caused by other causes than Chagas disease) and 897
<jats:italic>T. cruzi</jats:italic>
<jats:underline>seropositive</jats:underline>
samples (684 CC and 213 IND). 1870 peptides were increased in
<jats:italic>T. cruzi</jats:italic>
seropositive IgG compared to
<jats:italic>T. cruzi</jats:italic>
seronegative samples. Peptides from Nucleoporin NUP149, a flagellar attachment zone protein, basal body protein, surface protein TolT and cytoskeleton associated protein were the peptides with highest IgG response. Using as little as 5 peptides, I derived a classifier model for
<jats:italic>T. cruzi</jats:italic>
infection with 97% accuracy. Then, I compared CC and IND samples using logistic regression models after splitting our sample into 2 cohort groups. From these, 316 peptides were significantly different between CC and IND: 289 peptides were increased in CC (27% of them belong to the trans-sialidase class) and 27 peptides were increased in IND (FDR>0.01). Aiming to develop a classifier to separate CCC from IND, I analyzed our data using machine learning approaches. LASSO returned the best model using 48 peptides, with 70% of accuracy, 74% of sensitivity and 69% of specificity. The peptides selected for the model belong to 38 proteins, 21% being unknow function proteins, 18% trans-sialidases, 8% flagellar associated proteins, and 60S ribosomal protein, Nucleoporins and R27-2 proteins classes representing 5% each. Ninety (90%) of selected peptides in LASSO were identified in the previous results using the logistic regression model. I showed for the first time that Chagas Cardiomyopathy individuals have a differential IgG profile against
<jats:italic>T. cruzi</jats:italic>
proteins compared to IND individuals. I described a differential IgG response against 84 sequences (62 increased in CCC and 22 increased in IND) that can be related to disease development.
</jats:p>