MMP-2 and MMP-9 plasma levels are potential biomarkers for indeterminate and cardiac clinical forms progression in chronic Chagas disease

Figures

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  Figure 1. Matrix metalloproteinases (MMP)-2 and MMP-9 plasma levels over time. Paired points graphs demonstrated concentration (pg/mL) of MMP-2 (A) and MMP-9 (B) in plasma from non-infected individuals (NI, white, n = 5), patients with indeterminate (IND, gray, n = 15) and cardiac (CARD, dark gray, n = 11) clinical forms of Chagas disease, and from patients that had evolution of clinical forms during the cohort (EV, blue, n = 2). Proportion graphs demonstrated median for time zero (T0, black) over median for time one (T1, checkered). Statistical differences (p ≤ 0.05) between times were obtained by Wilcoxon signed-rank test and Mann-Whitney test, showed by asterisk (*).

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  Figure 2. Tissue inhibitor of metalloproteinases (TIMP) plasma levels over time. Paired points graphs demonstrated concentration (pg/mL) of TIMP-1 (A) TIMP-2 (B) TIMP-3©, and TIMP-4 (D) in plasma from non-infected individuals (NI, white, n = 5), patients with indeterminate (IND, gray, n = 15) and cardiac (CARD, dark gray, n = 11) clinical forms of Chagas disease, and from patients that had evolution of clinical forms during the cohort (EV, blue, n = 2). Proportion graphs demonstrated median for time zero (T0, black) over median for time one (T1, checkered). Statistical differences (p ≤ 0.05) between times were obtained by Wilcoxon signed-rank test and Mann-Whitney test, showed by asterisk (*).

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  Figure 3. Low and high producers for Matrix metalloproteinases (MMP) and Tissue inhibitor of metalloproteinases (TIMP). Heatmaps demonstrated low (red), median (black), and high (blues) producers for MMP-2, -9, TIMP-1, -2, -3 and -4. Groups were separated into non-infected individuals (NI, n = 5), patients with indeterminate (IND, n = 15) and cardiac (CARD, n = 11) clinical forms of Chagas disease, and from patients that had evolution of clinical forms during the cohort (EV, n = 2). For each group, two boxes are demonstrated: upper box indicates time zero (T0) and lower box indicates time one (T1). The numbers identify the patient.

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  Figure 4. Percentage of high producers. Calculated percentage of high producers for non-infected individuals (NI, n = 5), patients with indeterminate (IND, n = 15) and cardiac (CARD, n = 11) clinical forms of Chagas disease, and from patients that had evolution of clinical forms during the cohort (EV, n = 2) was represented as a curve graph. The solid line showed the percentage of high producers in time zero (T0) and the dotted line the time one (T1) per group.

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  Figure 5. Biomarker performance measurement. Receiver Operating Characteristics (ROC) curve analysis was calculated to determine the potential for plasma MMP-2 and MMP-9 levels to segregate: (A) non-infected individuals (NI) from patients with indeterminate (IND) clinical form; (B) NI from patients with cardiac (CARD) clinical form; and (C) IND from CARD patients. All percentage values to sensitivity and specificity were shown. The measure of separability was demonstrated by the area under the curve (AUC) with 95% confidence interval. Statistical significance (p ≤ 0.05) was showed by asterisk (*).