Adult, Antigens, CD, Biomarkers, Cell Adhesion Molecules, Neuronal, Cystic Fibrosis, Disease Progression, Enzyme-Linked Immunosorbent Assay, Female, Fetal Proteins, Humans, Male, Neutrophils, Proteomics, Young Adult, alpha 1-Antitrypsin
US Alpha-1 Foundation, The Medical Research Charities Group/Health Research Board, and the Program for Research in Third Level Institutes (PRTLI) administered by the Higher Education Authority
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 14 days (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
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.
Medicine and Health Sciences
Reeves EP, Bergin DA, Fitzgerald S, Hayes E, Keenan J, Henry M, Meleady P, Vega-Carrascal I, Murray MA, Low TB, McCarthy C, O'Brien E, Clynes M, Gunaratnam C, McElvaney NG. A novel neutrophil derived inflammatory biomarker of pulmonary exacerbation in cystic fibrosis. Journal of Cystic Fibros. 2012;11(2):100-7
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