Inflammatory and cardiac biomarkers are differentially expressed in clinical stages of Chagas disease.
BACKGROUND
Chagas disease has a long clinically silent period following Trypanosoma cruzi infection and before development of overt clinical pathology; detectable biomarkers of infection and pathogenesis are urgently needed. We tested 22 biomarkers known to be associated with cardiomyopathy to evaluate if a biomarker signature could successfully classify T. cruzi seropositive subjects into clinical Chagas disease stage groups.


METHODS
This cross-sectional retrospective case-control study enrolled T. cruzi seropositive blood donors (BD) who were further characterized as having chronic Chagas cardiomyopathy (CC-BD) or not (nonCC-BD) and seronegative (SN) control donors; we also included clinically diagnosed Chagas cardiomyopathy patients (CC-P). All subjects underwent a health history questionnaire, medical examination, electro- and echocardiograms (ECG and Echo) and phlebotomy. Biomarkers were measured on blinded samples by luminex bead array and Ortho VITROS.


RESULTS
A clear biomarker pattern was observed only in more severe cardiac disease; this pattern included significantly elevated levels of inflammatory cytokines IFN-γ, IL-6, IL-10 and TNF-α and soluble cardiovascular disease biomarkers CK-MB, troponin, myoglobin, VCAM and NTproBNP while there were lower levels of MPO, PAI-1, and MCP-1. The markers determined to be the most predictive of disease by ROC curve analysis were NTproBNP and T. cruzi PCR status.


CONCLUSIONS
Although many biomarkers demonstrated increased or decreased concentrations among the clinical forms of Chagas disease, NTproBNP and T. cruzi PCR were the only tests that would independently be of clinical value for disease staging, in concert with ECG, Echo and clinical assessments.
Blood Systems Research Institute, San Francisco, CA, United States; Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA, United States.
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SM
Keating
Blood Systems Research Institute, San Francisco, CA, United States; Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA, United States.
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X
Deng
Heart Institute (InCor) da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
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Fernandes
Hospital das Clínicas and Faculdade de Medicina, Universidade Federal de Minas Gerais, Minas Gerais, Brazil; Heart Institute (InCor) da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil; Division of Clinical Immunology and Allergy, University of São Paulo School of Medicine, São Paulo, SP 06504-000, Brazil.
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Cunha-Neto
Hospital das Clínicas and Faculdade de Medicina, Universidade Federal de Minas Gerais, Minas Gerais, Brazil.
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Ribeiro
Blood Systems Research Institute, San Francisco, CA, United States.
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Adesina
Blood Systems Research Institute, San Francisco, CA, United States.
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Beyer
Ortho Clinical Diagnostics, Rochester, NY, United States.
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Contestable
Blood Systems Research Institute, San Francisco, CA, United States; Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA, United States.
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B
Custer
Blood Systems Research Institute, San Francisco, CA, United States; Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA, United States. Electronic address: mbusch@bloodsystems.org.
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MP
Busch
Department of Infectious Disease and Institute of Tropical Medicine, University of São Paulo, São Paulo, Brazil.
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Sabino
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D001782:Blood Donors; D016022:Case-Control Studies; D002598:Chagas Cardiomyopathy / Q000097:blood* / Q000473:pathology / Q000628:therapy; D018925:Chemokines / Q000097:blood; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000097:blood*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007249:Inflammation / Q000097:blood / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D012189:Retrospective Studies; D014349:Trypanosoma cruzi / Q000302:isolation & purification; D055815:Young Adult
D015415:Biomarkers; D018925:Chemokines; D016207:Cytokines; D010446:Peptide Fragments; D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain
Cardiomyopathy; Chemokines; Cytokines; Inflammation; Trypanosoma cruzi (T. cruzi)