sTREM-1 is elevated in cystic fibrosis and correlates with proteases

Forrester, D.L.; Barr, Helen L.; Fogarty, A.; Knox, A.

Abstract

Background: sTREM-1 (soluble triggering receptor expressed on myeloid cells-1) is a novel inflammatory marker that may be of clinical use in cystic fibrosis (CF). Dysregulation of the TREM pathway has been demonstrated in other inflammatory diseases and modulation in animal models has therapeutic benefit. We hypothesised that sTREM-1 could act as a biomarker of disease in cystic fibrosis.

Methods: Plasma from 17 patients with CF (stable and pre and post pulmonary exacerbation) and eight healthy volunteers was analyzed for sTREM-1 and proteases (matrix metalloproteinase-8 (MMP-8), MMP-9, and human neutrophil elastase HNE).

Results: sTREM-1 Levels were elevated in stable CF subjects compared to controls (148 pg/ml (130–160) [median(IQR)] vs. 87 (55–118) (P < 0.01)) but were not further increased during pulmonary exacerbation nor decreased after antibiotic treatment in CF. Protease levels were increased in CF plasma compared to controls: MMP–8 = 3.1 ng/ml (1.5–7.6) vs. 0.3 (0.18–0.53) (P < 0.01) (Wilcoxon); MMP–9 = 170 ng/ml (124–282) vs. 49 (39–90) (P <  0.01); HNE = 30.2 ng/ml (22.7–30.9) vs. 17.5 (11.2–22.2) (P < 0.05). sTREM-1 correlated positively with protease levels lnMMP-8 r2 = 0.55 (P = 0.08), lnMMP-9 r2 =  0.61(P < 0.05), lnHNE r2 = 0.35 (P < 0.05).

Conclusions: sTREM-1 is constitutively elevated in CF and positively correlates with protease levels. Modulation of this pathway may be of therapeutic benefit to patients with CF.

Citation

Forrester, D., Barr, H. L., Fogarty, A., & Knox, A. (2017). sTREM-1 is elevated in cystic fibrosis and correlates with proteases. Pediatric Pulmonology, 52(4), 467-471. https://doi.org/10.1002/ppul.23650

• Journal Article Type: Article
• Acceptance Date: Nov 17, 2016
• Online Publication Date: Jan 9, 2017
• Publication Date: 2017-04
• Deposit Date: Jul 12, 2017
• Publicly Available Date: Jul 12, 2017
• Journal: Pediatric Pulmonology
• Print ISSN: 8755-6863
• Electronic ISSN: 1099-0496
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 52
• Issue: 4
• Pages: 467-471
• DOI: https://doi.org/10.1002/ppul.23650
• Keywords: inflammation, MMPs, biomarkers
• Public URL: https://nottingham-repository.worktribe.com/output/841156
• Publisher URL: http://onlinelibrary.wiley.com/doi/10.1002/ppul.23650/abstract
• Additional Information: This is the peer reviewed version of the following article: Forrester, D.L., Barr, H.L., Fogarty, A. and Knox, A. (2017), sTREM-1 is elevated in cystic fibrosis and correlates with proteases. Pediatric Pulmonology, 52: 467–471., which has been published in final form at http://dx.doi.org/10.1002/ppul.23650. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
• Contract Date: Jul 12, 2017