PMID- 33134491
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220418
IS  - 2373-8731 (Print)
IS  - 2373-8731 (Electronic)
IS  - 2373-8731 (Linking)
VI  - 6
IP  - 11
DP  - 2020 Nov
TI  - Circulating Donor Heart Exosome Profiling Enables Noninvasive Detection of 
      Antibody-mediated Rejection.
PG  - e615
LID - 10.1097/TXD.0000000000001057 [doi]
LID - e615
AB  - BACKGROUND: Endomyocardial biopsy remains the gold standard for distinguishing 
      types of immunologic injury-acute versus antibody-mediated rejection (AMR). 
      Exosomes are tissue-specific extracellular microvesicles released by many cell 
      types, including transplanted heart. Circulating transplant heart exosomes 
      express donor-specific human leukocyte antigen (HLA) I molecules. As AMR is 
      mediated by antibodies to donor HLAs, we proposed that complement deposition that 
      occurs with AMR at tissue level would also occur on circulating donor heart 
      exosomes. METHODS: Plasma exosomes in 4 patients were isolated by column 
      chromatography and ultracentrifugation. Donor heart exosomes were purified using 
      anti-donor HLA I antibody beads and complement C4d protein expression was 
      assessed in this subset as marker for AMR. RESULTS: Three patients had no 
      rejection episodes. Circulating donor heart exosomes showed troponin protein and 
      mRNA expression at all follow-up time points. One patient developed AMR on day 14 
      endomyocardial biopsy that was treated with rituximab, IVIG/plasmapheresis. 
      Time-specific detection of C4d protein was seen in donor heart exosome subset in 
      this patient, which resolved with treatment. C4d was not seen in other 3 
      patients' donor exosomes. CONCLUSIONS: Anti-donor HLA I specificity enables 
      characterization of circulating donor heart exosomes in the clinical setting. 
      Further characterization may open the window to noninvasively diagnose rejection 
      type, such as AMR.
CI  - Copyright (c) 2020 The Author(s). Transplantation Direct. Published by Wolters 
      Kluwer Health, Inc.
FAU - Hu, Robert W
AU  - Hu RW
AD  - Department of Surgery, University of Pennsylvania Perelman School of Medicine, 
      Philadelphia, PA.
FAU - Korutla, Laxminarayana
AU  - Korutla L
AD  - Department of Surgery, University of Pennsylvania Perelman School of Medicine, 
      Philadelphia, PA.
FAU - Reddy, Sanjana
AU  - Reddy S
AD  - Department of Surgery, University of Pennsylvania Perelman School of Medicine, 
      Philadelphia, PA.
FAU - Harmon, Joey
AU  - Harmon J
AD  - Department of Surgery, University of Pennsylvania Perelman School of Medicine, 
      Philadelphia, PA.
FAU - Zielinski, Patrick D
AU  - Zielinski PD
AD  - Department of Surgery, University of Pennsylvania Perelman School of Medicine, 
      Philadelphia, PA.
FAU - Bueker, Alex
AU  - Bueker A
AD  - Department of Surgery, University of Pennsylvania Perelman School of Medicine, 
      Philadelphia, PA.
FAU - Molina, Maria
AU  - Molina M
AD  - Division of Cardiology, Department of Medicine, University of Pennsylvania 
      Perelman School of Medicine, Philadelphia, PA.
FAU - Romano, Connie
AU  - Romano C
AD  - Division of Cardiology, Department of Medicine, University of Pennsylvania 
      Perelman School of Medicine, Philadelphia, PA.
FAU - Margulies, Ken
AU  - Margulies K
AD  - Division of Cardiology, Department of Medicine, University of Pennsylvania 
      Perelman School of Medicine, Philadelphia, PA.
FAU - McLean, Rhondalyn
AU  - McLean R
AD  - Division of Cardiology, Department of Medicine, University of Pennsylvania 
      Perelman School of Medicine, Philadelphia, PA.
FAU - Lal, Priti
AU  - Lal P
AD  - Department of Pathology, University of Pennsylvania Perelman School of Medicine, 
      Philadelphia, PA.
FAU - Vallabhajosyula, Prashanth
AU  - Vallabhajosyula P
AD  - Division of Cardiac Surgery, Department of Surgery, Yale University School of 
      Medicine, New Haven, CT.
LA  - eng
GR  - K08 HL132099/HL/NHLBI NIH HHS/United States
GR  - UL1 TR001863/TR/NCATS NIH HHS/United States
PT  - Journal Article
DEP - 20201019
PL  - United States
TA  - Transplant Direct
JT  - Transplantation direct
JID - 101651609
PMC - PMC7575166
COIS- The authors declare no conflicts of interest.
EDAT- 2020/11/03 06:00
MHDA- 2020/11/03 06:01
PMCR- 2020/10/19
CRDT- 2020/11/02 06:21
PHST- 2020/06/22 00:00 [received]
PHST- 2020/07/28 00:00 [revised]
PHST- 2020/08/05 00:00 [accepted]
PHST- 2020/11/02 06:21 [entrez]
PHST- 2020/11/03 06:00 [pubmed]
PHST- 2020/11/03 06:01 [medline]
PHST- 2020/10/19 00:00 [pmc-release]
AID - 10.1097/TXD.0000000000001057 [doi]
PST - epublish
SO  - Transplant Direct. 2020 Oct 19;6(11):e615. doi: 10.1097/TXD.0000000000001057. 
      eCollection 2020 Nov.