Abstract We076: Humoral profile of individuals with Chagas Cardiomyopathy
Bibliographic record
Abstract
Chronic Chagas cardiomyopathy (CCC) is the most severe manifestation of Chagas disease and one of the main causes of cardiomyopathy in Latin America. The number of individuals infected with Trypanosoma cruzi (T. cruzi), the causative parasite of Chagas disease, exceeds 6 million, with an increasing presence in non-endemic regions such as Europe, Japan, Canada, and the USA. While approximately 70% of infected individuals remain asymptomatic and are categorized as indeterminate (IND), the remaining 30% develop cardiac manifestations several decades after the initial infection. Despite extensive efforts to elucidate the triggers and predictors underlying the progression from IND to CCC, the exact causative factors remain elusive. Hypotheses have been proposed that focus on the specific humoral response, including the production of antibodies that effectively neutralize the parasite or demonstrate cross-reactivity between parasite and cardiac proteins. Here, using PhIP-seq technology we comprehensively characterized the IgG profile of 897 T. cruzi seropositive individuals. We identified 628 epitopes with increased IgG reactivity in chronic T. cruzi seropositive individuals. Mucin TcMUCII, trans-sialidase, and MASP emerged as the primary classes of proteins showing elevated IgG response. Remarkably, the serum of CCC individuals showed robustly elevated reactivity against 84 epitopes compared to IND individuals, while IgG response against 23 epitopes was increased in the serum of IND individuals. Trans-sialidase and mucin-like glycoproteins were the main classes of proteins distinguishing these two groups. Among all epitopes with increased reactivity in the serum of CCC individuals compared to IND, 36 epitopes showed linear sequence similarity to 210 human proteins highly expressed in human heart. These included sarcomere structural proteins, suggesting potential cross-reactions between the antibodies targeting T. cruzi epitopes and proteins with key roles in cardiac function. Overall, our study describes the humoral landscape of Chagas disease, expanding the pool of potential candidates for future vaccine development or as targets for infection/trials efficiency monitoring. Additionally, we identified potential sources of antibody cross-reaction that may contribute to CCC progression, including epitopes sharing sequence similarities with key proteins involved in cardiac structure.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".