دورية أكاديمية
أعرض في EDS

Relationship between donor-derived cell-free DNA and tissue-based rejection-related transcripts in heart transplantation.

التفاصيل البيبلوغرافية
العنوان: Relationship between donor-derived cell-free DNA and tissue-based rejection-related transcripts in heart transplantation.
المؤلفون: Lee DH; Heart Transplant Program, Transplant Institute, Tampa General Hospital, Tampa, Florida; Division of Cardiovascular Medicine, Department of Internal Medicine, University of South Florida Morsani College of Medicine, Tampa, Florida; Heart & Vascular Institute, Tampa General Hospital, Tampa, Florida. Electronic address: daehyunlee@usf.edu., Usmani A; Morsani College of Medicine, University of South Florida, Tampa, Florida., Wu R; Heart Transplant Program, Transplant Institute, Tampa General Hospital, Tampa, Florida; Division of Cardiovascular Medicine, Department of Internal Medicine, University of South Florida Morsani College of Medicine, Tampa, Florida; Heart & Vascular Institute, Tampa General Hospital, Tampa, Florida., Wicks T; Heart Transplant Program, Transplant Institute, Tampa General Hospital, Tampa, Florida; Heart & Vascular Institute, Tampa General Hospital, Tampa, Florida., Noh CY; Department of Pediatrics, Children's Hospital Los Angeles, USC Keck School of Medicine, Los Angeles, California., Burke R; CareDx, San Francisco, California., Ravichandran V; CareDx, San Francisco, California., Wolf-Doty T; CareDx, San Francisco, California., Dumitru I; Heart Transplant Program, Transplant Institute, Tampa General Hospital, Tampa, Florida; Division of Cardiovascular Medicine, Department of Internal Medicine, University of South Florida Morsani College of Medicine, Tampa, Florida; Heart & Vascular Institute, Tampa General Hospital, Tampa, Florida., Oliveira GH; Heart Transplant Program, Transplant Institute, Tampa General Hospital, Tampa, Florida; Division of Cardiovascular Medicine, Department of Internal Medicine, University of South Florida Morsani College of Medicine, Tampa, Florida; Heart & Vascular Institute, Tampa General Hospital, Tampa, Florida., Berman P; Heart Transplant Program, Transplant Institute, Tampa General Hospital, Tampa, Florida; Division of Cardiovascular Medicine, Department of Internal Medicine, University of South Florida Morsani College of Medicine, Tampa, Florida; Heart & Vascular Institute, Tampa General Hospital, Tampa, Florida., Mackie B; Heart Transplant Program, Transplant Institute, Tampa General Hospital, Tampa, Florida; Division of Cardiovascular Medicine, Department of Internal Medicine, University of South Florida Morsani College of Medicine, Tampa, Florida; Heart & Vascular Institute, Tampa General Hospital, Tampa, Florida. Electronic address: bmackie@tgmg.org.
المصدر: The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation [J Heart Lung Transplant] 2024 Jul; Vol. 43 (7), pp. 1118-1125. Date of Electronic Publication: 2024 Feb 17.
نوع المنشور: Journal Article; Observational Study
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: United States NLM ID: 9102703 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1557-3117 (Electronic) Linking ISSN: 10532498 NLM ISO Abbreviation: J Heart Lung Transplant Subsets: MEDLINE
أسماء مطبوعة: Publication: 1999- : New York, NY : Elsevier
Original Publication: St. Louis, Mo. : Mosby-Year Book, Inc., c1991-
مواضيع طبية MeSH: Heart Transplantation* , Graft Rejection*/diagnosis , Cell-Free Nucleic Acids*/blood , Tissue Donors*, Retrospective Studies ; Male ; Humans ; Middle Aged ; Female ; Adult ; Biopsy ; Myocardium/pathology ; Myocardium/metabolism
مستخلص: Background: Endomyocardial biopsy (EMB)-based traditional microscopy remains the gold standard for the detection of cardiac allograft rejection, despite its limitation of inherent subjectivity leading to inter-reader variability. Alternative techniques now exist to surveil for allograft injury and classify rejection. Donor-derived cell-free DNA (dd-cfDNA) testing is now a validated blood-based assay used to surveil for allograft injury. The molecular microscope diagnostic system (MMDx) utilizes intragraft rejection-associated transcripts (RATs) to classify allograft rejection and identify injury. The use of dd-cfDNA and MMDx together provides objective molecular insight into allograft injury and rejection. The aim of this study was to measure the diagnostic agreement between dd-cfDNA and MMDx and assess the relationship between dd-cfDNA and MMDx-derived RATs, which may provide further insight into the pathophysiology of allograft rejection and injury.
Methods: This is a retrospective observational study of 156 EMB evaluated with traditional microscopy and MMDx. All samples were paired with dd-cfDNA from peripheral blood before EMB (up to 9 days). Diagnostic agreement between traditional histopathology, MMDx, and dd-cfDNA (threshold of 0.20%) was compared for assessment of allograft injury. In addition, the relationship between dd-cfDNA and individual RAT expression levels from MMDx was evaluated.
Results: MMDx characterized allograft tissue as no rejection (62.8%), antibody-mediated rejection (ABMR) (26.9%), T-cell-mediated rejection (TCMR) (5.8%), and mixed ABMR/TCMR (4.5%). For the diagnosis of any type of rejection (TCMR, ABMR, and mixed rejection), there was substantial agreement between MMDx and dd-cfDNA (76.3% agreement). All transcript clusters (group of gene sets designated by MMDx) and individual transcripts considered abnormal from MMDx had significantly elevated dd-cfDNA. In addition, a positive correlation between dd-cfDNA levels and certain MMDx-derived RATs was observed. Tissue transcript clusters were correlated with dd-cfDNA scores, including DSAST, GRIT, HT1, QCMAT, and S4. For individual transcripts, tissue ROBO4 was significantly correlated with dd-cfDNA in both nonrejection and rejection as assessed by MMDx.
Conclusions: Collectively, we have shown substantial diagnostic agreement between dd-cfDNA and MMDx. Furthermore, based on the findings presented, we postulate a common pathway between the release of dd-cfDNA and expression of ROBO4 (a vascular endothelial-specific gene that stabilizes the vasculature) in the setting of antibody-mediated rejection, which may provide a mechanistic rationale for observed elevations in dd-cfDNA in AMR, compared to acute cellular rejection.
(Copyright © 2024. Published by Elsevier Inc.)
فهرسة مساهمة: Keywords: acute cellular rejection; alograft rejection; antibody-mediated rejection; donor-derived cell-free DNA; gene expression profile; heart transplant; molecular microscopy
المشرفين على المادة: 0 (Cell-Free Nucleic Acids)
تواريخ الأحداث: Date Created: 20240219 Date Completed: 20240601 Latest Revision: 20240614
رمز التحديث: 20240614
DOI: 10.1016/j.healun.2024.02.011
PMID: 38373559
قاعدة البيانات: MEDLINE
الوصف
تدمد:1557-3117
DOI:10.1016/j.healun.2024.02.011