PMID- 32665078
OWN - NLM
STAT- MEDLINE
DCOM- 20210831
LR  - 20210831
IS  - 1557-3117 (Electronic)
IS  - 1053-2498 (Linking)
VI  - 39
IP  - 10
DP  - 2020 Oct
TI  - Circulating extracellular vesicles as non-invasive biomarker of rejection in 
      heart transplant.
PG  - 1136-1148
LID - S1053-2498(20)31610-7 [pii]
LID - 10.1016/j.healun.2020.06.011 [doi]
AB  - BACKGROUND: Circulating extracellular vesicles (EVs) are raising considerable 
      interest as a non-invasive diagnostic tool, as they are easily detectable in 
      biologic fluids and contain a specific set of nucleic acids, proteins, and lipids 
      reflecting pathophysiologic conditions. We aimed to investigate differences in 
      plasma-derived EV surface protein profiles as a biomarker to be used in 
      combination with endomyocardial biopsies (EMBs) for the diagnosis of allograft 
      rejection. METHODS: Plasma was collected from 90 patients (53 training cohort, 37 
      validation cohort) before EMB. EV concentration was assessed by nanoparticle 
      tracking analysis. EV surface antigens were measured using a multiplex flow 
      cytometry assay composed of 37 fluorescently labeled capture bead populations 
      coated with specific antibodies directed against respective EV surface epitopes. 
      RESULTS: The concentration of EVs was significantly increased and their diameter 
      decreased in patients undergoing rejection as compared with negative ones. The 
      trend was highly significant for both antibody-mediated rejection and acute 
      cellular rejection (p < 0.001). Among EV surface markers, CD3, CD2, ROR1, SSEA-4, 
      human leukocyte antigen (HLA)-I, and CD41b were identified as discriminants 
      between controls and acute cellular rejection, whereas HLA-II, CD326, CD19, CD25, 
      CD20, ROR1, SSEA-4, HLA-I, and CD41b discriminated controls from patients with 
      antibody-mediated rejection. Receiver operating characteristics curves confirmed 
      a reliable diagnostic performance for each single marker (area under the curve 
      range, 0.727-0.939). According to differential EV-marker expression, a diagnostic 
      model was built and validated in an external cohort of patients. Our model was 
      able to distinguish patients undergoing rejection from those without rejection. 
      The accuracy at validation in an independent external cohort reached 86.5%. Its 
      application for patient management has the potential to reduce the number of 
      EMBs. Further studies in a higher number of patients are required to validate 
      this approach for clinical purposes. CONCLUSIONS: Circulating EVs are highly 
      promising as a new tool to characterize cardiac allograft rejection and to be 
      complementary to EMB monitoring.
CI  - Copyright (c) 2020 International Society for Heart and Lung Transplantation. 
      Published by Elsevier Inc. All rights reserved.
FAU - Castellani, Chiara
AU  - Castellani C
AD  - Cardiovascular Pathology and Pathological Anatomy, Department of Cardiac, 
      Thoracic, Vascular Sciences and Public Health, University of Padova, Padova, 
      Italy.
FAU - Burrello, Jacopo
AU  - Burrello J
AD  - Laboratory of Cellular and Molecular Cardiology and Laboratory for Cardiovascular 
      Theranostics, Cardiocentro Ticino Foundation, Lugano, Switzerland.
FAU - Fedrigo, Marny
AU  - Fedrigo M
AD  - Cardiovascular Pathology and Pathological Anatomy, Department of Cardiac, 
      Thoracic, Vascular Sciences and Public Health, University of Padova, Padova, 
      Italy.
FAU - Burrello, Alessio
AU  - Burrello A
AD  - Department of Electrical, Electronic and Information Engineering "Guglielmo 
      Marconi" (DEI), University of Bologna, Bologna, Italy.
FAU - Bolis, Sara
AU  - Bolis S
AD  - Laboratory of Cellular and Molecular Cardiology and Laboratory for Cardiovascular 
      Theranostics, Cardiocentro Ticino Foundation, Lugano, Switzerland.
FAU - Di Silvestre, Dario
AU  - Di Silvestre D
AD  - Proteomics and Metabolomic Laboratory, ITB-CNR, Segrate, Italy.
FAU - Tona, Francesco
AU  - Tona F
AD  - Division of Cardiac Surgery, Department of Cardiac, Thoracic, Vascular Sciences 
      and Public Health, University of Padua, Padua, Italy.
FAU - Bottio, Tomaso
AU  - Bottio T
AD  - Division of Cardiac Surgery, Department of Cardiac, Thoracic, Vascular Sciences 
      and Public Health, University of Padua, Padua, Italy.
FAU - Biemmi, Vanessa
AU  - Biemmi V
AD  - Laboratory of Cellular and Molecular Cardiology and Laboratory for Cardiovascular 
      Theranostics, Cardiocentro Ticino Foundation, Lugano, Switzerland; Faculty of 
      Biomedical Sciences, Universita Svizzera Italiana, Lugano, Switzerland.
FAU - Toscano, Giuseppe
AU  - Toscano G
AD  - Division of Cardiac Surgery, Department of Cardiac, Thoracic, Vascular Sciences 
      and Public Health, University of Padua, Padua, Italy.
FAU - Gerosa, Gino
AU  - Gerosa G
AD  - Division of Cardiac Surgery, Department of Cardiac, Thoracic, Vascular Sciences 
      and Public Health, University of Padua, Padua, Italy.
FAU - Thiene, Gaetano
AU  - Thiene G
AD  - Cardiovascular Pathology and Pathological Anatomy, Department of Cardiac, 
      Thoracic, Vascular Sciences and Public Health, University of Padova, Padova, 
      Italy.
FAU - Basso, Cristina
AU  - Basso C
AD  - Cardiovascular Pathology and Pathological Anatomy, Department of Cardiac, 
      Thoracic, Vascular Sciences and Public Health, University of Padova, Padova, 
      Italy.
FAU - Longnus, Sarah L
AU  - Longnus SL
AD  - Department of Cardiovascular Surgery, Inselspital, Bern University Hospital, 
      Bern, Switzerland.
FAU - Vassalli, Giuseppe
AU  - Vassalli G
AD  - Laboratory of Cellular and Molecular Cardiology and Laboratory for Cardiovascular 
      Theranostics, Cardiocentro Ticino Foundation, Lugano, Switzerland; Faculty of 
      Biomedical Sciences, Universita Svizzera Italiana, Lugano, Switzerland.
FAU - Angelini, Annalisa
AU  - Angelini A
AD  - Cardiovascular Pathology and Pathological Anatomy, Department of Cardiac, 
      Thoracic, Vascular Sciences and Public Health, University of Padova, Padova, 
      Italy. Electronic address: annalisa.angelini@unipd.it.
FAU - Barile, Lucio
AU  - Barile L
AD  - Laboratory of Cellular and Molecular Cardiology and Laboratory for Cardiovascular 
      Theranostics, Cardiocentro Ticino Foundation, Lugano, Switzerland; Faculty of 
      Biomedical Sciences, Universita Svizzera Italiana, Lugano, Switzerland; Institute 
      of Life Science, Scuola Superiore Sant'Anna, Pisa, Italy. Electronic address: 
      lucio.barile@cardiocentro.org.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200620
PL  - United States
TA  - J Heart Lung Transplant
JT  - The Journal of heart and lung transplantation : the official publication of the 
      International Society for Heart Transplantation
JID - 9102703
RN  - 0 (Biomarkers)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Allografts
MH  - Biomarkers/blood
MH  - Biopsy
MH  - Extracellular Vesicles/*metabolism
MH  - Female
MH  - Flow Cytometry
MH  - Graft Rejection/*blood/diagnosis
MH  - Heart Transplantation/*adverse effects
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - ROC Curve
OTO - NOTNLM
OT  - allograft rejection
OT  - biomarker
OT  - extracellular vesicles
OT  - heart transplant
OT  - machine learning
EDAT- 2020/07/16 06:00
MHDA- 2021/09/01 06:00
CRDT- 2020/07/16 06:00
PHST- 2020/03/23 00:00 [received]
PHST- 2020/06/02 00:00 [revised]
PHST- 2020/06/16 00:00 [accepted]
PHST- 2020/07/16 06:00 [pubmed]
PHST- 2021/09/01 06:00 [medline]
PHST- 2020/07/16 06:00 [entrez]
AID - S1053-2498(20)31610-7 [pii]
AID - 10.1016/j.healun.2020.06.011 [doi]
PST - ppublish
SO  - J Heart Lung Transplant. 2020 Oct;39(10):1136-1148. doi: 
      10.1016/j.healun.2020.06.011. Epub 2020 Jun 20.