Evidence map›Paper›PMID 33134491›Full record

ArticleTransplantation direct2020

Circulating Donor Heart Exosome Profiling Enables Noninvasive Detection of Antibody-mediated Rejection.

Robert W Hu, Laxminarayana Korutla, Sanjana Reddy, Joey Harmon, Patrick D Zielinski, Alex Bueker, Maria Molina, Connie Romano, Ken Margulies, Rhondalyn McLean and 2 more

Open access · goldAbstract read
In one paragraph

Article in Transplantation direct, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.6field-weighted citation impact, top 16% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 14 citations in OpenAlex.

  1. Review
  2. Exosomes as a biomarker in postoperative complications: a literature review.Frontiers in cell and developmental biology · 2026
    Review
  3. Circulating T cell specific extracellular vesicle profiles in cardiac allograft acute cellular rejection.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2024
    Article
  4. Review
  5. Review
  6. Review
  7. Circulating microRNAs in cellular and antibody-mediated heart transplant rejection.The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2022
    Article
  8. Review
  9. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 2 institutions in 1 country.

Robert W HuDepartment of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
Laxminarayana KorutlaDepartment of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
Sanjana ReddyDepartment of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
Joey HarmonDepartment of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
Patrick D ZielinskiDepartment of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
Alex BuekerDepartment of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
Maria MolinaDivision of Cardiology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
Connie RomanoDivision of Cardiology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
Ken MarguliesDivision of Cardiology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
Rhondalyn McLeanDivision of Cardiology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
Priti LalDepartment of Pathology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
Prashanth VallabhajosyulaDivision of Cardiac Surgery, Department of Surgery, Yale University School of Medicine, New Haven, CT.
University of Pennsylvania · USYale University · US

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Donor specific extracellular vesicle characterization for monitoring lung transplant rejectionK08HL132099 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI VALLABHAJOSYULA, PRASHANTH · 2017 to 2019
$509k
NCATS NIH HHS UL1 TR001863NHLBI NIH HHS K08 HL132099
6 · The paper itself

Abstract

backgroundEndomyocardial 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.

methodsPlasma 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.

resultsThree 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.

conclusionsAnti-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.

Identifiers

PMID33134491
PMCPMC7575166
OpenAlexW3095180065

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.