| Biomarkers |
Relevance and/or validity in chagasic cardiomyopathy (CC) |
References |
| Tumor necrosis factor (TNF), atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and pro-BNP |
↑ BNP, TNF, and pro-BNP or TNF-related to depression of LVEF, with ↑ of LV end-diastolic diameter and with LV premature complexes ↑ ANP and ↑ BNP correlated with worsening ECHO parameters, predict death and demand for heart transplant ROC-based analyses: BNP (280.4 pg/ml) with 96% of sensitivity and 75% of specificity for predicting E/E’ >15 BNP (60 pg/ml or more) has sensitivity of 91.7% and specificity of 82.8% for LV dysfunction prediction. |
(3131. Moreira MCV, Heringer-Walther S, Wessel N, Ventura TM, Wang Y, Schultheiss HP, et al. Prognostic value of natriuretic peptides in Chagas'disease: a 3-year follow-up investigation. Cardiology. 2008; 110(4): 217-25.,3232. Talvani A, Rocha MOC, Barcelos LS, Gomes YM, Ribeiro AL, Teixeira MM. Elevated concentrations of CCL2 and tumor necrosis factor-alpha in chagasic cardiomyopathy. Clin Infect Dis. 2004; 38(7): 943-50.,3333. Oliveira BMR, Botoni FA, Ribeiro ALP, Pinto AS, Reis AM, Nunes MCP, et al. Correlation between BNP levels and Doppler echocardiographic parameters of left ventricle filling pressure in patients with Chagasic cardiomyopathy. Echocardiography. 2009; 26(5): 521-7.,3434. Ribeiro ALP, Teixeira MM, Reis AM, Talvani A, Perez AA, Barros MVL, et al. Brain natriuretic peptide based strategy to detect left ventricular dysfunction in Chagas disease: a comparison with the conventional approach. Int J Cardiol. 2006; 109(1): 34-40.,3535. Gomes JAS, Araújo FF, Vitelli-Avelar DM, Sathler-Avelar R, Lage PS, Wendling APB, et al. Expression, impaired regulatory cytokine microenvironment interfaced with Anti-Trypanosoma cruzi IgG reactivity in cardiac Chagas disease patients. Front Microbiol. 2018; 9: 1608.) |
| ɣ-interferon (IFN-γ), IL-1, IL-6, IL-12, IL-17andIL-13. Creatine-kinase (CK-MB) isoenzyme Matrix metalloproteinase (MMP-2 and MMP-9); tissue inhibitor of the MMP (TIMP-2) |
↑ levels IFN-γ IL-6, IL-12, IL-13, CK-MB, MMP-2, MMP-9, TIMP-2 and (↓ IL10 and IL-17) related to severe CC ↑MMP-9 as for late fibrosis and severe cardiac remodeling ROC-based analyses: ↑MMP-2/MMP-9 ratio related to ECG abnormalities. |
(3636. Keating SM, Deng X, Fernandes F, Cunha-Neto E, Ribeiro AL, Adesina B, et al. Inflammatory and cardiac biomarkers are differentially expressed in clinical stages of Chagas disease. Int J Cardiol. 2015; 199: 451-9.,3737. Okamoto EE, Sherbuk JE, Clark EH, Marks MA, Gandarilla O, Galdos-Cardenas G, et al. Biomarkers in Trypanosoma cruzi-infected and uninfected individuals with varying severity of cardiomyopathy in Santa Cruz, Bolivia. PLoS Negl Trop Dis. 2014; 8: e3362.,3838. Medeiros NI, Gomes JAS, Fiuza JA, Sousa GR, Almeida EF, Novaes RO, et al. MMP-2 and MMP-9 plasma levels are potential biomarkers for indeterminate and cardiac clinical forms progression in chronic Chagas disease. Sci Rep. 2019; 9(1): 14170.,3939. Bautista-López NL, Morillo CA, López-Jaramillo P, Quiroz R, Luengas C, Silva SY, et al. Matrix metalloproteinases 2 and 9 as diagnostic markers in the progression to Chagas cardiomyopathy. Am Heart J. 2013; 165: 558-66.,4040. Tobar IB, Parra F, Pérez CN, Rodríguez-Bonfante C, Useche F, Bonfante-Cabarcas R. Prevalence of Trypanosoma cruzi antibodies and inflammatory markers in uncompensated heart failure. Rev Soc Bras Med Trop. 2011; 44(6): 691-6.) (4141. Guedes PMM, Gutierrez FRS, Silva GK, Dellalibera-Joviliano R, Rodrigues GJ, Bendhack LM, et al. Deficient regulatory T cell activity and low frequency of IL-17-producing T cells correlate with the extent of cardiomyopathy in human Chagas'disease. PLoS Negl Trop Dis. 2012; 6(4): e1630.,4242. Sousa GR, Gomes JAS, Fares RCG, Damásio MPS, Chaves AT, Ferreira KS, et al. Plasma cytokine expression is associated with cardiac morbidity in Chagas disease. PLoS One. 2014; 9(3): e87082.,4343. Gómez-Olarte S, Bolaños NI, Echeverry M, Rodrígues AN, Cuéllar A, Puerta CJ, et al. intermediate monocytes and cytokine production associated with severe forms of Chagas disease. Front Immunol. 2019; 19(10): 1671.,4444. Alba-Alvarado MD, Salazar-Schettino PM, Jiménez-Álvarez L, Cabrera-Bravo M, García-Sancho C, Zenteno E, et al. Th-17 cytokines are associated with severity of Trypanosoma cruzi chronic infection in pediatric patients from endemic areas of Mexico. Acta Trop. 2018; 178: 134.,4545. Bestetti RB, Dellalibera-Joviliano R, Lopes GS, Faria-Jr M, Furlan-Daniel R, Lopes KC, et al. Determination of the Th1, Th2, Th17, and Treg cytokine profile in patients with chronic Chagas heart disease and systemic arterial hypertension. Heart Vessels. 2019; 34(1): 123-133.) |
| Vinculin, plasminogen and NK/CD8+ T-cell MiR-19a-3p, miR-21-5p, and miR-29b-3p CC - CXC chemokine receptors (CXCR3, CCR4, 5, 7 and 8) and ligandsCXCL9 and 10) CD1D and Programmed cell death (PD-1/PDL1) |
↑ myosin (light chain 2 and heavy chain 11), ↑ levels of vinculin and plasminogen and ↑ NK/CD8+T-cell correlated to the cardiac dysfunction ↑ expression of MiR-19a-3p, miR-21-5p, and miR-29b-3p correlated with cardiac dysfunction and fibrosis ↑ CXCL9, CXCR3, CCR4, CCR5, CCR7, CCR8, CD1D and PD-1/PDL1 expression correlated with myocarditis and/or LV worsening ↓ genotypic frequencies of CXCL9 (rs10336CC) andCXCL10(rs3921GG), and ↑CCR5(rs1799988CC) correlated with LV dysfunction.
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(4646. Ferreira LRP, Ferreira FM, Nakaya HI, Deng X, Cândido DS, Oliveira LC, et al. Blood gene signatures of Chagas cardiomyopathy with or without ventricular dysfunction. J Infect Dis. 2017; 215(3): 387-95.,4747. Wen JJ, Zago MP, Nuñez S, Gupta S, Burgos FN, Garg NJ. Serum proteomic signature of human chagasic patients for the identification of novel potential protein biomarkers of disease. Mol Cell Proteomics. 2012; 11(8): 435-52.,4848. Nonaka CKV, Macêdo CT, Cavalcante BRR, Alcântara AC, Silva DN, Bezerra MR, et al. Circulating miRNAs as potential biomarkers associated with cardiac remodeling and fibrosis in Chagas disease cardiomyopathy. Int J Mol Sci. 2019; 20(16): 4064.,4949. Nogueira LG, Santos RHB, Ianni BM, Fiorelli AI, Mairena EC, Benvenuti LA, et al. Myocardial chemo kine expression and intensity of myocarditis in Chagas cardiomyopathy are controlled by polymorphisms in CXCL9 and CXCL10. PLoS Negl Trop Dis. 2012; 6(10): e1867.)(5050. Passos LSA, Villani FNA, Magalhães LMD, Gollob KJ, Antonelli LRV, Nunes MCP, et al. Blocking of CD1d decreases Trypanosoma cruzi-induced activation of CD4-CD8- T Cells and modulates the inflammatory response in patients with Chagas heart disease. J Infect Dis. 2016; 214(6): 935-44.,5151. Damasio MPS, Rocha MOC, Sousa GR, Ferreira KS, Fares-Gusmão RCG, Medeiros NI, et al. PD1 and PDL1 molecules control suppressor activity of regulatory T cells in chronic Chagas cardiomyopathy patients. Immunol. 2019; 80(7): 517-22.) |
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