A novel neutrophil derived inflammatory biomarker of pulmonary exacerbation in cystic fibrosis

Reeves, Emer P.; Bergin, David A.; Fitzgerald, Sean; Hayes, Elaine; Keenan, Joanne; Henry, Michael; Meleady, Paula; Vega-Carrascal, Isabel; Murray, Michelle A.; Low, Teck Boon; McCarthy, Cormac; O'Brien, Emmet; Clynes, Martin; Gunaratnam, Cedric; McElvaney, Noel G.

doi:10.1016/j.jcf.2011.09.010

« Previous Next »Journal of Cystic Fibrosis
Volume 11, Issue 2 , Pages 100-107, March 2012

A novel neutrophil derived inflammatory biomarker of pulmonary exacerbation in cystic fibrosis

Emer P. Reeves
- Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland
- Contributed equally to this work.
- Corresponding author. Tel.: +353 1 8093877; fax: +353 1 8093808.
David A. Bergin
- Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland
- Contributed equally to this work.
Sean Fitzgerald
- Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland
Elaine Hayes
- Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland
Joanne Keenan
- National Institute for Cellular Biotechnology, Dublin City University, Glasnevin, Dublin 9, Ireland
Michael Henry
- National Institute for Cellular Biotechnology, Dublin City University, Glasnevin, Dublin 9, Ireland
Paula Meleady
- National Institute for Cellular Biotechnology, Dublin City University, Glasnevin, Dublin 9, Ireland
Isabel Vega-Carrascal
- Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland
Michelle A. Murray
- Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland
Teck Boon Low
- Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland
Cormac McCarthy
- Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland
Emmet O'Brien
- Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland
Martin Clynes
- National Institute for Cellular Biotechnology, Dublin City University, Glasnevin, Dublin 9, Ireland
Cedric Gunaratnam
- Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland
Noel G. McElvaney
- Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland

Received 22 July 2011; received in revised form 21 September 2011; accepted 27 September 2011. published online 31 October 2011.

Abstract

Background

The focus of this study was to characterize a novel biomarker for cystic fibrosis (CF) that could reflect exacerbations of the disease and could be useful for therapeutic stratification of patients, or for testing of potential drug treatments. This study focused exclusively on a protein complex containing alpha-1 antitrypsin and CD16b (AAT:CD16b) which is released into the bloodstream from membranes of pro-inflammatory primed neutrophils.

Methods

Neutrophil membrane expression and extracellular levels of AAT and CD16b were quantified by flow cytometry, Western blot analysis and by 2D-PAGE. Interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha) and AAT:CD16b complex were quantified in CF plasma (n=38), samples post antibiotic treatment for 14days (n=10), chronic obstructive pulmonary disease (n=10), AAT deficient (n=10) and healthy control (n=14) plasma samples by ELISA.

Results

Cell priming with IL-8 and TNF-alpha caused release of the AAT:CD16b complex from the neutrophil cell membrane. Circulating plasma levels of IL-8, TNF-alpha and AAT:CD16b complex were significantly higher in patients with CF than in the other patient groups or healthy controls (P<0.05). Antibiotic treatment of pulmonary exacerbation in patients with CF led to decreased plasma protein concentrations of AAT:CD16b complex with a significant correlation with improved FEV1 (r=0.81, P=0.003).

Conclusion

The results of this study have shown that levels of AAT:CD16b complex present in plasma correlate to the inflammatory status of patients. The AAT:CD16b biomarker may become a useful addition to the clinical diagnosis of exacerbations in CF.

Keywords: Cystic fibrosis, Alpha-1 antitrypsin, CD16b, Infection, Inflammation, Pulmonary exacerbation