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Soluble markers of the Toll-like receptor 4 pathway differentiate between active and latent tuberculosis and are associated with treatment responses.

Feruglio SL, Trøseid M, Damås JK, Kvale D, Dyrhol-Riise AM - PLoS ONE (2013)

Bottom Line: In contrast, sCD14 levels increased after 2 weeks (p = 0.047) with a subsequent modest decrease throughout the treatment period.There was no significant difference in concentrations of any of these markers between patients with pulmonary and extrapulmonary TB or between patients with or without symptoms.A decline in LPS and MD-2 concentrations was associated with response to anti-TB treatment.

View Article: PubMed Central - PubMed

Affiliation: Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.

ABSTRACT

Background: Biomarkers to differentiate between active tuberculosis (TB) and latent TB infection (LTBI) and to monitor treatment responses are requested to complement TB diagnostics and control, particularly in patients with multi-drug resistant TB. We have studied soluble markers of the Toll-like-receptor 4 (TLR-4) pathway in various stages of TB disease and during anti-TB treatment.

Methods: Plasma samples from patients with culture confirmed drug-sensitive TB (n = 19) were collected before and after 2, 8 and 24 weeks of efficient anti-TB treatment and in a LTBI group (n = 6). Soluble (s) CD14 and myeloid differentiation-2 (MD-2) were analyzed by the Enzyme-linked immunosorbent assay (ELISA). Lipopolysaccharide (LPS) was analyzed by the Limulus Amebocyte Lysate colorimetric assay. Nonparametric statistics were applied.

Results: Plasma levels of sCD14 (p<0.001), MD-2 (p = 0.036) and LPS (p = 0.069) were elevated at baseline in patients with untreated active TB compared to the LTBI group. MD-2 concentrations decreased after 2 weeks of treatment (p = 0.011), while LPS levels decreased after 8 weeks (p = 0.005). In contrast, sCD14 levels increased after 2 weeks (p = 0.047) with a subsequent modest decrease throughout the treatment period. There was no significant difference in concentrations of any of these markers between patients with pulmonary and extrapulmonary TB or between patients with or without symptoms.

Conclusion: Our data suggest that plasma levels of LPS, MD-2 and sCD14 can discriminate between active TB and LTBI. A decline in LPS and MD-2 concentrations was associated with response to anti-TB treatment. The clinical potential of these soluble TLR-4 pathway proteins needs to be further explored.

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Related in: MedlinePlus

sCD14 levels at various stages of TB infection and during therapy.Soluble CD14 concentrations (ng/ml) in plasma from A) patients with LTBI (n = 6) and active TB (n = 19) at baseline and after 8 and 24 weeks of anti-TB therapy and B) active TB (n = 10) at baseline and after 2 weeks of anti-TB therapy. Horizontal lines represent the median values. Significant p values (<.05) between groups and time-points are indicated.
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pone-0069896-g004: sCD14 levels at various stages of TB infection and during therapy.Soluble CD14 concentrations (ng/ml) in plasma from A) patients with LTBI (n = 6) and active TB (n = 19) at baseline and after 8 and 24 weeks of anti-TB therapy and B) active TB (n = 10) at baseline and after 2 weeks of anti-TB therapy. Horizontal lines represent the median values. Significant p values (<.05) between groups and time-points are indicated.

Mentions: Plasma levels of sCD14 at baseline were higher in the active TB group compared to the LTBI group (2320 ng/ml [1990–3720] vs. 1335 ng/ml [1190–1450], p<0.001) (Fig. 4A). After 2 weeks of therapy there was a significant increase in sCD14 in the active TB group (2820 ng/ml [2190–3650], p = 0.047) (Fig. 4B). A slightly decrease in median sCD14 was observed after 24 weeks of therapy (2220 ng/ml [1920–2800]), although not significant (p = 0.064) (Fig. 4A). sCD14 levels did not differ between patients with pulmonary and extrapulmonary TB (2450 ng/ml [2200–3720] vs. 2240 ng/mL [1640–2475]).


Soluble markers of the Toll-like receptor 4 pathway differentiate between active and latent tuberculosis and are associated with treatment responses.

Feruglio SL, Trøseid M, Damås JK, Kvale D, Dyrhol-Riise AM - PLoS ONE (2013)

sCD14 levels at various stages of TB infection and during therapy.Soluble CD14 concentrations (ng/ml) in plasma from A) patients with LTBI (n = 6) and active TB (n = 19) at baseline and after 8 and 24 weeks of anti-TB therapy and B) active TB (n = 10) at baseline and after 2 weeks of anti-TB therapy. Horizontal lines represent the median values. Significant p values (<.05) between groups and time-points are indicated.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3713063&req=5

pone-0069896-g004: sCD14 levels at various stages of TB infection and during therapy.Soluble CD14 concentrations (ng/ml) in plasma from A) patients with LTBI (n = 6) and active TB (n = 19) at baseline and after 8 and 24 weeks of anti-TB therapy and B) active TB (n = 10) at baseline and after 2 weeks of anti-TB therapy. Horizontal lines represent the median values. Significant p values (<.05) between groups and time-points are indicated.
Mentions: Plasma levels of sCD14 at baseline were higher in the active TB group compared to the LTBI group (2320 ng/ml [1990–3720] vs. 1335 ng/ml [1190–1450], p<0.001) (Fig. 4A). After 2 weeks of therapy there was a significant increase in sCD14 in the active TB group (2820 ng/ml [2190–3650], p = 0.047) (Fig. 4B). A slightly decrease in median sCD14 was observed after 24 weeks of therapy (2220 ng/ml [1920–2800]), although not significant (p = 0.064) (Fig. 4A). sCD14 levels did not differ between patients with pulmonary and extrapulmonary TB (2450 ng/ml [2200–3720] vs. 2240 ng/mL [1640–2475]).

Bottom Line: In contrast, sCD14 levels increased after 2 weeks (p = 0.047) with a subsequent modest decrease throughout the treatment period.There was no significant difference in concentrations of any of these markers between patients with pulmonary and extrapulmonary TB or between patients with or without symptoms.A decline in LPS and MD-2 concentrations was associated with response to anti-TB treatment.

View Article: PubMed Central - PubMed

Affiliation: Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.

ABSTRACT

Background: Biomarkers to differentiate between active tuberculosis (TB) and latent TB infection (LTBI) and to monitor treatment responses are requested to complement TB diagnostics and control, particularly in patients with multi-drug resistant TB. We have studied soluble markers of the Toll-like-receptor 4 (TLR-4) pathway in various stages of TB disease and during anti-TB treatment.

Methods: Plasma samples from patients with culture confirmed drug-sensitive TB (n = 19) were collected before and after 2, 8 and 24 weeks of efficient anti-TB treatment and in a LTBI group (n = 6). Soluble (s) CD14 and myeloid differentiation-2 (MD-2) were analyzed by the Enzyme-linked immunosorbent assay (ELISA). Lipopolysaccharide (LPS) was analyzed by the Limulus Amebocyte Lysate colorimetric assay. Nonparametric statistics were applied.

Results: Plasma levels of sCD14 (p<0.001), MD-2 (p = 0.036) and LPS (p = 0.069) were elevated at baseline in patients with untreated active TB compared to the LTBI group. MD-2 concentrations decreased after 2 weeks of treatment (p = 0.011), while LPS levels decreased after 8 weeks (p = 0.005). In contrast, sCD14 levels increased after 2 weeks (p = 0.047) with a subsequent modest decrease throughout the treatment period. There was no significant difference in concentrations of any of these markers between patients with pulmonary and extrapulmonary TB or between patients with or without symptoms.

Conclusion: Our data suggest that plasma levels of LPS, MD-2 and sCD14 can discriminate between active TB and LTBI. A decline in LPS and MD-2 concentrations was associated with response to anti-TB treatment. The clinical potential of these soluble TLR-4 pathway proteins needs to be further explored.

Show MeSH
Related in: MedlinePlus