Global Proteomics Analysis of Circulating
Extracellular Vesicles Isolated from Lung Transplant Recipients
Posted on 2020-06-12 - 18:34
Lung transplant recipients
(LTxRs) with acute rejection (AR) and chronic rejection (bronchiolitis
obliterans syndrome [BOS]) induce circulating exosomes known to contain
donor human leukocyte antigens and lung-associated self-antigens.
Here, we sought to identify proteomic signatures in circulating extracellular
vesicles (EVs) that differentiate LTxRs in 4 groups: stable, AR, BOS,
or respiratory viral infection (RVI). EVs were isolated from plasma
from patients in each group via ultracentrifugation. EV protein cargoes
were prepared for shotgun proteomics using liquid chromatography–tandem
mass spectrometry. We identified 2 unique proteins for AR, 4 for RVI,
24 for BOS, and 8 for stable LTxRs. Differential analysis of AR, BOS,
RVI, and stable proteins identified significantly deregulated proteins
(p < 0.05, log2(fold change) > ±1)
in each condition (31, 2, and 2, respectively). EVs from LTxRs with
AR contained proteins involved in immunoglobulin, complement regulation,
coagulation, and innate and adaptive immune response pathways. EVs
from LTxRs with BOS revealed enriched immunoglobulin receptors and
a carboxypeptidase N catalytic chain. EVs from LTxRs with RVI had
an enriched macrophage-stimulating factor. We found unique signatures
in LTxRs with AR, BOS, and RVI, highlighting complex immune mechanisms
underlying lung allograft rejection. Proteomic signatures in LTxRs’
circulating EVs provided insights into immunological mechanisms of
graft rejection and RVI.
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Bansal, Sandhya; McGilvrey, Marissa; Garcia-Mansfield, Krystine; Sharma, Ritin; Bremner, Ross M.; Smith, Michael A.; et al. (2020). Global Proteomics Analysis of Circulating
Extracellular Vesicles Isolated from Lung Transplant Recipients. ACS Publications. Collection. https://doi.org/10.1021/acsomega.0c00859
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AUTHORS (9)
SB
Sandhya Bansal
MM
Marissa McGilvrey
KG
Krystine Garcia-Mansfield
RS
Ritin Sharma
RB
Ross M. Bremner
MS
Michael A. Smith
RH
Ramsey Hachem
PP
Patrick Pirrotte
TM
Thalachallour Mohanakumar
KEYWORDS
shotgun proteomicsBOSCirculating Extracellular VesiclesDifferential analysisRVIresponse pathwaysLTxRextracellular vesiclesmacrophage-stimulating factorProteomic signaturesproteomic signaturesgraft rejectionlung allograft rejectionimmunoglobulin receptorsGlobal Proteomics Analysis4 groupsleukocyte antigenscarboxypeptidase Nbronchiolitis obliterans syndromelung-associated self-antigenscomplement regulationEV protein cargoesLung Transplant Recipients Lung transplant recipientsAR