The pleural proteome in lung transplant recipients and non-transplant patients

<bold>Introduction:</bold> Pleural effusions occur frequently after lung transplantation (LTX), often remain unclear despite thorough clinical workup and are associated with increased mortality after transplantation. <bold>Methods:</bold> Pleural effusions were analyzed using LC mass spectrometry based proteomics. Analysis of protein abundancies was performed using linear mixed effects models. <bold>Results:</bold> In total 81 pleural effusions were analyzed, 47 effusions were obtained from LTX recipients, 34 effusions from non-transplant patients. Using an in-depth clinical phenotyping approach with serum chemistry, pleural effusion chemistry, pleural effusion differential cell count, microbiological and histopathological results available, we were able to dissect relevant confounders of the pleural proteome. Kidney failure, trans-/exudate dichotomy, previous thoracic surgery and status post transplantation were found to be independent determinants of the pleural proteome composition. We identified a protein pattern unique to pleural effusions of LTX recipients with an upregulation of proteins linked to ECM deposition and a downregulation of mesothelial markers, adjusted for pleural effusion etiology, kidney failure and previous thoracic surgery. <bold>Conclusions:</bold> For the first time, these data demonstrate the necessity of adjusting for kidney failure and previous thoracic surgery as confounder of pleural effusion proteome changes, independent of transudate/exudate classification. Our study suggests an active disease process implicated in the pathogenesis of LTX pleural effusions that involves a decrease in pleural mesothelial cells and an increase in activated pleural fibroblasts, potentially by mesothelial-to-mesenchymal transition.