• Aric L Gregson, Aki Hoji, Patil Injean, Steven T Poynter, Claudia Briones, Vyacheslav Palchevskiy, S Sam Weigt, Michael Y Shino, Ariss Derhovanessian, David Sayah, Rajan Saggar, David Ross, Abbas Ardehali, Joseph P Lynch, and John A Belperio.
• 1 Division of Infectious Diseases, Department of Medicine.
• Am. J. Respir. Crit. Care Med. 2015 Dec 15;192(12):1490-503.

RationaleThe mechanism by which acute allograft rejection leads to chronic rejection remains poorly understood despite its common occurrence. Exosomes, membrane vesicles released from cells within the lung allograft, contain a diverse array of biomolecules that closely reflect the biologic state of the cell and tissue from which they are released. Exosome transcriptomes may provide a better understanding of the rejection process. Furthermore, biomarkers originating from this transcriptome could provide timely and sensitive detection of acute cellular rejection (AR), reducing the incidence of severe AR and chronic lung allograft dysfunction and improving outcomes.ObjectivesTo provide an in-depth analysis of the bronchoalveolar lavage fluid exosomal shuttle RNA population after lung transplantation and evaluate for differential expression between acute AR and quiescence.MethodsSerial bronchoalveolar lavage specimens were ultracentrifuged to obtain the exosomal pellet for RNA extraction, on which RNA-Seq was performed.Measurements And Main ResultsAR demonstrates an intense inflammatory environment, skewed toward both innate and adaptive immune responses. Novel, potential upstream regulators identified offer potential therapeutic targets.ConclusionsOur findings validate bronchoalveolar lavage fluid exosomal shuttle RNA as a source for understanding the pathophysiology of AR and for biomarker discovery in lung transplantation.

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