Proteomic Profiling of Circulating Extracellular Vesicles Isolated from Human Lung Transplant Recipients

S. Bansal¹, M. McGilvrey², K. Garcia-Mansfield², R. Sharma², R. Bremner¹, M. Smith¹, R. Hachem³, P. Pirrotte², T. Mohanakumar¹

¹Norton Thoracic Institute, St. Joseph’s Hospital and Medical Center, Phoenix, AZ, ²Translational Genomics Research Institute (TGen), Collaborative Center for Translational Mass Spectrometry (CCTMS), Phoenix, AZ, ³Department of Medicine, Washington University School of Medicine, Phoenix, AZ

Meeting: 2020 American Transplant Congress

Abstract number: A-334

Keywords: Infection, Lung transplantation, Rejection

Session Information

Session Name: Poster Session A: Biomarker Discovery and Immune Modulation

Session Type: Poster Session

Date: Saturday, May 30, 2020

Session Time: 3:15pm-4:00pm

Presentation Time: 3:30pm-4:00pm

Location: Virtual

*Purpose: Circulating exosomes in human lung transplant recipients (LTxRs) with acute (AR) and chronic rejection (bronchiolitis obliterans syndrome [BOS]) contain donor human leukocyte antigen (HLA) and lung self-antigens (SAgs), Kα1 Tubulin (Kα1T) and Collagen V (Col-V), costimulatory molecules (CD80, CD86), transcription factors NFkB and 20S proteasome (Am J Transplant 17(2):474-484). In this study we identified unique proteomic signatures in circulating extracellular vesicles (EVs) that can differentiate human LTxRs with AR, BOS, respiratory viral infection (RVI) and stable.

*Methods: We isolated EVs (stable, AR, BOS or RVI) using ultracentrifugation from plasma of human LTxRs and characterized them for the presence of lung SAgs (Kα1T and Col-V). EV protein cargoes were prepared for shotgun proteomics using liquid chromatography-tandem mass spectrometry (LC-MS/MS).

*Results: Unique proteins were identified in each clinical subgroup: 2 for AR, 24 for BOS, 4 for RVI and 8 in the stable cohort using MS/MS. Differential analysis of the proteins from AR, BOS and RVI compared to stable yielded significant unique proteins (p-value<.05, fold-change>2) in each clinical cohorts:


Clinical Group	Number of Unique Proteins	Related Functions
AR vs Stable	27	Complement regulation, innate and adaptive immune response pathways
BOS vs Stable	2	Immunoglobulin receptors and carboxypeptidase N catalytic chain
RVI vs Stable	2	Macrophage stimulating factor

*Conclusions: To conclude proteomic signatures of circulating EVs from LTxRs provided insights into immunological mechanisms at play in graft rejection as well as RVI leading to increased risk for chronic lung allograft dysfunction.

To cite this abstract in AMA style:

Bansal S, McGilvrey M, Garcia-Mansfield K, Sharma R, Bremner R, Smith M, Hachem R, Pirrotte P, Mohanakumar T. Proteomic Profiling of Circulating Extracellular Vesicles Isolated from Human Lung Transplant Recipients [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/proteomic-profiling-of-circulating-extracellular-vesicles-isolated-from-human-lung-transplant-recipients/. Accessed November 22, 2024.

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