Effect of TB Treatment on Neutrophil-Derived Soluble Inflammatory Mediators in TB Patients with and without HIV Coinfection

Abstract

The mycobacteriological analysis of sputum samples is the gold standard for tuberculosis diagnosis and treatment monitoring. However, sputum production can be challenging after the initiation of TB treatment. As a possible alternative, we therefore investigated the dynamics of neutrophil-derived soluble inflammatory mediators during TB treatment in relation to HIV ART status and the severity of lung impairment. Plasma samples of TB patients with (N = 47) and without HIV (N = 21) were analyzed at baseline, month 2, month 6 (end of TB treatment) and month 12. Plasma levels of MMP-1, MMP-8, MPO and S100A8 markedly decreased over the course of TB treatment and remained at similar levels thereafter. Post-TB treatment initiation, significantly elevated plasma levels of MMP-8 were detected in TB patients living with HIV, especially if they were not receiving ART treatment at baseline. Our data confirm that the plasma levels of neutrophil-based biomarkers can be used as candidate surrogate markers for TB treatment outcome and HIV-infection influenced MMP-8 and S100A8 levels. Future studies to validate our results and to understand the dynamics of neutrophils-based biomarkers post-TB treatment are needed.

Keywords: TB; TB treatment; multiplex; patients living with HIV.

Figure 1

Dynamic changes in the concentrations of neutrophil-related inflammatory biomarkers upon TB treatment initiation. The concentrations of the biomarkers MMP-1 (A), MMP-2 (B), MMP-8 (C), S100A8 (D) and MPO (E) in all subjects (n = 68) at baseline (n = 62), 2 months (n = 56), 6 months (n = 59) and 12 months (n = 42) after TB treatment initiation are shown. Bars represent medians and interquartile range. Statistical analyses were performed using the Kruskal–Wallis and the Wilcoxon signed rank test for paired samples. A p-value of < 0.05 was considered significant.

Figure 2

Comparisons of neutrophil-related inflammatory biomarkers MMP-1 (A), MMP-2 (B), MMP-8 (C), S100A8 (D) and MPO (E) between TB mono-infected (n = 21, green dots), HIV/TB coinfected patients on ART (n = 23, blue dots) and HIV/TB coinfected ART-naïve patients (n = 19, red dots) at baseline, month 2, month 6 and month 12 study visits. The magenta dots are the subjects with drug-resistant TB. Bars represent the median and interquartile range. The Mann–Whitney test was used for comparisons between the groups at different time points. p < 0.05 was considered significant.

Figure 3

Comparisons of plasmatic biomarkers based on spirometry results from before TB treatment or on day 14: MMP-1 (A), MMP-2 (B), MMP-8 (C), S100A8 (D) and MPO (E) at baseline (n = 29), month 2 (n = 29), month 6 (n = 30) and month 12 (n = 17) between less (n = 16, blue dots) and more severe (n = 18, red dots) lung impairment. The more and less severe lung-impaired patients are represented by red and blue circles, respectively. The magenta dots represent the subjects with drug-resistant TB. Bars represent the median and interquartile range. Mann–Whitney tests were used for comparisons between the groups at different time points. p < 0.05 was considered significant.

Figure 4

Comparisons of plasmatic biomarkers based on spirometry results of month 6: MMP-1 (A), MMP-2 (B), MMP-8 (C), S100A8 (D) and MPO (E) at baseline (n = 45), month 2 (n = 42), month 6 (n = 48) and month 12 (n = 31) between patients with more severe (n = 18) and less severe (n = 33) lung impairment. The more and less severe lung-impaired patients are represented by red and blue circles, respectively. The magenta dots represent the subjects with drug-resistant TB. (F) MMP-8 and MPO plasma levels at baseline of subjects with less and more severe lung impairment based on spirometry results at month 6, with red dots coding for subjects with more severe lung impairment at baseline. Bars represent the median and interquartile range. Mann–Whitney tests were used for comparisons between the groups at different time points. p < 0.05 was considered significant.