Molecular mechanisms involved in rejection following human lung transplantation are not well understood. Goal of this study is to identify proteomic signatures in the circulating exosomes isolated from human lung transplant recipients with clinical conditions, i.e, stable, acute rejection, chronic rejection (Bronchiolitis Obliterans Syndrome (BOS)) and respiratory viral infections requiring interventions. Our analysis using bioinformatics tools identified unique proteins exclusive for each set and were consistent in availability in all sample replicates by Kruskal-Wallis Test and corrected by Benjamini-Hochberg correction. After removing high abundant proteins with <20% variation, proteins unique to each subset identified are: 29 in acute rejection (i.e. Ig lambda-3 chain C regions IGLC3; B cell receptor signaling, complement activation, innate immune response, cathelicidin antimicrobial peptide; humoral immune responses to bacterial and fungal infections, inflammatory response, innate immune response and regulation of IL8), 15 in BOS patients (i.e, UDP-glucose 6-dehydrogenase; involved in biosynthesis of glycosaminoglycans, Lysosome-associated membrane glycoprotein 1; involved in regulation of Nk cell degranulation), 15 in stable patients (i.e, LPS/IL-1 mediated functions such as regulation of chemokine synthesis, Carboxypeptidase N subunit 2; enzyme for protein stabilization, Proteasome subunit beta type-9; antigen processing and presentation, T cell receptor and TNF mediated signaling pathways), and 84 in viral infected patients (i.e, IL-8; involved in chemokine signaling and immune response, F9, PPBP;chemoattractant and activator of neutrophils). We further analyzed the levels of commonly identified peptides within different groups and determined fold change values. To unify the representation of genes we performed Gene Ontology analysis (GO) and condition specific GO terms in different set of samples, i.e, (acute rejection 16, viral 226, stable 7, and BOS 0). In summary, unique proteins identified in clinical conditions are associated with immune response, response to wound healing and blood coagulation pathways which can play essential role in pathophysiology following lung transplantation.

CITATION INFORMATION: Bansal S., Pirrotte P., Saltzman M., Garcia K., Sharma M., Gunasekaran M., Smith M., Bremner R., Mohanakumar T. Identification of Exosomal Proteins from Human Lung Transplant Recipients Am J Transplant. 2017;17 (suppl 3).

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