Myriad Applications of Circulating Cell-Free DNA in Precision Organ Transplant Monitoring

Burnham, Philip; Khush, Kiran K.; Vlaminck, Iwijn De

doi:10.1513/annalsats.201608-634mg

Cited by 38 publications

(29 citation statements)

References 29 publications

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“…31,32 However, an increased cfDNA content was not specific to malignancies; elevated levels were also detected in the plasma of pregnant women and in patients that received transplantations. 33,34 Elevated cfDNA might also reflect physiological (e.g., exercise) 35,36 and non-malignant pathological processes, 7 such as inflammation, diabetes, tissue trauma, sepsis, and myocardial infarction. [37][38][39] The concentration of cfDNA in blood varies significantly; it ranges between 0-5 and >1000 ng/ml in patients with cancer and between 0 and 100 ng/ml in healthy subjects.…”

Section: Introductionmentioning

confidence: 99%

Life and death of circulating cell-free DNA

Kustanovich

Schwartz

Peretz

et al. 2019

Cancer Biology & Therapy

381

386

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Tumor-specific, circulating cell-free DNA in liquid biopsies is a promising source of biomarkers for minimally invasive serial monitoring of treatment responses in cancer management. We will review the current understanding of the origin of circulating cell-free DNA and different forms of DNA release (including various types of cell death and active secretion processes) and clearance routes. The dynamics of extracellular DNA in blood during therapy and the role of circulating DNA in pathophysiological processes (tumor-associated inflammation, NETosis, and pre-metastatic niche development) provide insights into the mechanisms that contribute to tumor development and metastases formation. Better knowledge of circulating tumor-specific cell-free DNA could facilitate the development of new therapeutic and diagnostic options for cancer management. ARTICLE HISTORY

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Section: Introductionmentioning

confidence: 99%

Life and death of circulating cell-free DNA

Kustanovich

Schwartz

Peretz

et al. 2019

Cancer Biology & Therapy

381

386

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“…Several research groups have studied the diagnostic role of donor-derived cell-free DNA for solid organ transplants including kidney, heart, liver and lung. 7 , 14 - 16 Allomap has been studied extensively, and is utilized in clinical practice, although it has not replaced EMB. 17 - 19 Combination of these platforms may provide adequate accuracy to help minimize the need for EMB-based monitoring.…”

Section: Discussionmentioning

confidence: 99%

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

Korutla

Reddy

et al. 2020

Transplantation Direct

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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.

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“…We first assayed 52 serial samples collected at short time intervals from five adult patients with COVID-19 that were treated at University of California, San Francisco (UCSF) Medical Center (median of 8 samples per patient [range [6][7][8][9][10][11][12][13][14][15][16][17][18]). These plasma samples were residual from clinical testing and were collected from this group of patients over a treatment time-period of up to 14 days with up to four samples collected within 24 hours (median time between consecutive collections of 13 hours [range 5-64]).…”

Section: Temporal Dynamics Of Cell-free Dna Tissues-of-origin In Plasmentioning

confidence: 99%

“…Since the advent of cfDNA based noninvasive prenatal testing, myriad applications of cfDNA in diagnostic medicine have been established [17]- [19]. These short fragments of circulating DNA are the debris of dead cells from across the body.…”

Section: Introductionmentioning

confidence: 99%

Cell-Free DNA in Blood Reveals Significant Cell, Tissue and Organ Specific injury and Predicts COVID-19 Severity

Cheng

Lenz

et al. 2020

Preprint

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COVID-19 primarily affects the lungs, but evidence of systemic disease with multi-organ involvement is emerging. Here, we developed a blood test to broadly quantify cell, tissue, and organ specific injury due to COVID-19, using genome-wide methylation profiling of circulating cell-free DNA in plasma. We assessed the utility of this test to identify subjects with severe disease in two independent, longitudinal cohorts of hospitalized patients. Cell-free DNA profiling was performed on 104 plasma samples from 33 COVID-19 patients and compared to samples from patients with other viral infections and healthy controls. We found evidence of injury to the lung and liver and involvement of red blood cell progenitors associated with severe COVID-19. The concentration of cfDNA correlated with the WHO ordinal scale for disease progression and was significantly increased in patients requiring intubation. This study points to the utility of cell-free DNA as an analyte to monitor and study COVID-19.

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Myriad Applications of Circulating Cell-Free DNA in Precision Organ Transplant Monitoring

Cited by 38 publications

References 29 publications

Life and death of circulating cell-free DNA

Life and death of circulating cell-free DNA

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

Cell-Free DNA in Blood Reveals Significant Cell, Tissue and Organ Specific injury and Predicts COVID-19 Severity

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