Altered Exosomal RNA Profiles in Bronchoalveolar Lavage from Lung Transplants with Acute Rejection

Journal Reference

Am J Respir Crit Care Med. 2015 Dec 15;192(12):1490-503.

Gregson AL¹, Hoji A², Injean P³, Poynter ST³, Briones C³, Palchevskiy V³, Sam Weigt S³, Shino MY³, Derhovanessian A³, Sayah D³, Saggar R³, Ross D³,Ardehali A⁴, Lynch JP 3rd³, Belperio JA³.

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Division of Infectious Diseases, Department of Medicine.
Department of Transplantation, University of Pittsburgh, Pittsburgh, Pennsylvania.
Division of Pulmonary, Critical Care, Allergy, and Immunology, Department of Medicine, and.
Division of Cardiothoracic Surgery, Department of Surgery, University of California, Los Angeles, California; and.

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Abstract

RATIONALE:

The 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 acute rejection and chronic lung allograft dysfunction and improving outcomes.

OBJECTIVES:

To 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.

METHODS:

Serial bronchoalveolar lavage specimens were ultracentrifuged to obtain the exosomal pellet for RNA extraction, on which RNA-Seq was performed.

MEASUREMENTS AND MAIN RESULTS:

Acute rejection demonstrates an intense inflammatory environment, skewed toward both innate and adaptive immune responses. Novel, potential upstream regulators identified offer potential therapeutic targets.

CONCLUSIONS:

Our findings validate bronchoalveolar lavage fluid exosomal shuttle RNA as a source for understanding the pathophysiology of acute rejection and for biomarker discovery in lung transplantation.

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