Blood and Site of Disease Inflammatory Profiles Differ in Patients With Pericardial Tuberculosis and Human Immunodeficiency Virus Type 1

Figure 1.. Analyte profiles in the different tuberculosis (TB) groups at baseline. A, Non-supervised 2-way hierarchical cluster analysis (Ward method) was employed to evaluate the TB groups using the 39 measured analytes (see Materials and Methods for expansions of abbreviations of analytes). TB status (pericardial TB [PCTB] in red, pulmonary TB [PTB] in blue, and latent TB infection [LTBI] in green) of each patient is indicated at the top of the dendrogram. Data are depicted as a heatmap colored from minimum to maximum normalized values for each marker. B, Principal component analysis on correlations based on the 39 analytes was used to explain the variance of the data distribution in the cohort. Each dot represents a participant. The 2 axes represent principal components 1 (PC1) and 2 (PC2). Their contribution to the total data variance is shown as a percentage. C, Analyte network analysis (Fruchterman-Reingold algorithm) in plasma of LTBI, PTB, and PCTB participants. Size of nodes indicates the number of connections. Size of edges indicates the Spearman r value (only r >0.6 was included). Blue lines: positive correlation. Red lines: negative correlation.

Figure 2.. Univariate associations between human immunodeficiency virus type 1 (HIV-1) viral load (VL) and analyte concentrations in the different tuberculosis (TB) groups. A, Spearman rank values of the univariate correlation between each analyte (see Materials and Methods for expansions of abbreviations of analytes) and the HIV-1 VL in plasma samples of participants with latent TB infection (LTBI), pulmonary TB (PTB), and pericardial TB (PCTB). Red bars indicate positive correlations, Black bars indicate negative correlations, and gray bars indicate nonsignificant correlations. B, Examples of IL-12p40 (maintained relationship between the TB groups) and IP-10 (disrupted relationship between the TB groups). The line indicates linear regression for statistically significant correlations.

Figure 3.. Analyte profiles in peripheral blood (plasma) and site of disease (pericardial fluid [PCF]) in participants with pericardial TB (PCTB). A, Nonsupervised 2-way hierarchical cluster analysis (HCA, Ward method) was employed to evaluate the 2 sites using the 39 analytes. The sample type and Mycobacterium tuberculosis (Mtb) culture results (PCF in purple; plasma in red; Mtb culture negative in white and positive in black) of each patient is indicated at the top of the dendrogram. Data are depicted as a heatmap colored from minimum to maximum normalized values detected for each marker. B, Principal component analysis on correlations based on the 39 analytes was used to explain the variance of the data distribution in the subgroup. Each dot represents a participant. The 2 axes represent principal components 1 (PC1) and 2 (PC2). Their contribution to the total data variance is shown as a percentage. C, Constellation plot-cluster analysis based on all measured analytes. Each dot represents a participant and is color-coded according to sample type. Each cluster obtained for the HCA is identified by a number. D, Pairwise correlation of the 39 analytes (see Materials and Methods for…

Figure 4.. Univariate associations between HLA-DR expression on Mycobacterium tuberculosis (Mtb)–specific CD4 T cells and analyte concentrations in the different tuberculosis (TB) groups. A, Representative flow cytometry plots of the expression of HLA-DR on Mtb-specific CD4 T cells. B, Expression of HLA-DR on Mtb-specific CD4 T cells in response to Mtb300. C, Spearman rank values of the univariate correlation between each analyte (see Materials and Methods for expansions of abbreviations of analytes) and between Mtb-specific CD4 T-cell activation (HLA-DR) level at the site of disease (pericardial fluid [PCF]) in participants with pericardial TB (PCTB), in blood of participants with PCTB and pulmonary TB (PTB), respectively. Red bars indicate a positive correlation, black bars indicate a negative correlation, and the gray bars indicate nonsignificant correlation. D, Representative graphs showing the positive (CCL1 and G-CSF) and negative (C4) correlation to HLA-DR frequency at the site of disease (PCF). Statistical comparisons were performed using a Kruskal-Wallis test, adjusted for multiple comparisons (Dunn test) for blood latent TB infection (LTBI) vs PTB vs PCTB, Wilcoxon test for blood…

Figure 5.. Analyte profiles in the different tuberculosis (TB) groups before, during, and after TB treatment. A, Nonsupervised 2-way hierarchical cluster analysis (Ward method) was employed to grade the TB groups using the 39 analytes (see Materials and Methods for expansions of abbreviations of analytes). TB status (pericardial TB [PCTB] in red, pulmonary TB [PTB] in blue, and latent TB infection [LTBI] in green) of each patient is indicated at the top of the dendrogram. Data are depicted as a heatmap colored from minimum to maximum normalized values detected for each marker. B, Principal component analysis on correlations based on the 39 analytes was used to explain the variance of the data distribution in the cohort. Each dot represents a participant. The 2 axes represent principal components 1 (PC1) and 2 (PC2). Their contribution to the total data variance is shown as a percentage. C, Representative graphs showing the change of concentrations of CXCL11, MIG, IL-6, and CRP with treatment and no statistical difference between week 24 (W24) post–treatment initiation and LTBI in both PTB and PCTB groups, respectively. Statistical comparisons were performed using a Friedman test, adjusted…