TY - JOUR T1 - Plasma protein profiling in alpha-1-antitrypsin deficiency JF - European Respiratory Journal JO - Eur Respir J VL - 38 IS - Suppl 55 SP - p4758 AU - Helen Stone AU - Douglas Ward AU - Robert Stockley Y1 - 2011/09/01 UR - http://erj.ersjournals.com/content/38/Suppl_55/p4758.abstract N2 - Introduction: Alpha-1-antitrypsin deficiency (ATD) results in an imbalance of proteases and antiproteases with proteolytic destruction of lung parenchyma, and subsequently early onset emphysema. We hypothesised changes in plasma peptides/proteins would be detectable and could provide potential biomarkers to predict a response to treatment in patients with ATD receiving augmentation therapy.Methods: Mass spectrometry was used to identify proteolytic fragments in plasma following neutrophil activation by ionophore or the addition of neutrophil elastase (NE). 72 paired plasma samples from the EXACTLE trial, taken at baseline and 6 months, were subsequently analysed using weak cation exchange beads and MALDI-TOF-MS, to determine whether any of the protein fragments generated in vitro were present in clinical samples and changed significantly in response to augmentation.Results: Following neutrophil activation or the addition of NE to plasma 325 peptides from 32 proteins were identified. 207 peptide peaks were detected in the spectra of the EXACTLE patients. T Tests were performed to determine whether or not the peak intensities of the peptides changed with treatment. Of these, 12 were significantly different in the treatment group, yet unchanged in the placebo group. The most significant of these had a p value of 2.08E-05.Conclusion: Changes in the plasma peptidome can be found in patient plasma after the addition of calcium ionophore and NE. Some of these changes can be detected in plasma pre/post augmentation. We aim to use more in depth proteomic approaches to further characterise changes in the plasma peptidome, and determine clinical utility as a guide to monitoring and treatment in ATD. ER -