Circulating Donor Heart Exosome Profiling Enables Noninvasive Detection of Antibody-mediated Rejection.
Journal
Transplantation direct
ISSN: 2373-8731
Titre abrégé: Transplant Direct
Pays: United States
ID NLM: 101651609
Informations de publication
Date de publication:
Nov 2020
Nov 2020
Historique:
received:
22
06
2020
revised:
28
07
2020
accepted:
05
08
2020
entrez:
2
11
2020
pubmed:
3
11
2020
medline:
3
11
2020
Statut:
epublish
Résumé
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. 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. 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. 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.
Sections du résumé
BACKGROUND
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
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
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
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.
Identifiants
pubmed: 33134491
doi: 10.1097/TXD.0000000000001057
pmc: PMC7575166
doi:
Types de publication
Journal Article
Langues
eng
Pagination
e615Subventions
Organisme : NHLBI NIH HHS
ID : K08 HL132099
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Informations de copyright
Copyright © 2020 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.
Déclaration de conflit d'intérêts
The authors declare no conflicts of interest.
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