Non-Invasive Monitoring of Infection and Rejection After Lung Transplantation

Vlaminck, Iwijn De; Martin, Lance; Kertesz, Michael A.; Patel, Kapil; Kowarsky, Mark; Strehl, Calvin; Cohen, Garrett; Luikart, Helen; Neff, Norma; Okamoto, Jennifer; Nicolls, M.; Cornfield, David N.; Weill, David; Valantine, Hannah A.; Khush, Kiran K.; Quake, Stephen R.

doi:10.1016/j.healun.2015.01.368

Cited by 7 publications

(11 citation statements)

References 22 publications

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“…There have been limited prior reports of the range and biological variation of dd-cfDNA levels in renal transplant recipients (2,18). Larger number of samples per patient have been analyzed in studies of heart and lung transplant recipients (4,5). These studies, however, have not provided analyses of biological variability (e.g., CV I , CV G , II, or RCV), and the data were mostly from recipients studied at single transplant centers, by using research-grade assays.…”

Section: Discussionmentioning

confidence: 99%

“…Observations of increased levels of ddcfDNA during acute rejection and correlation to severity of rejection have indicated the potential utility of dd-cfDNA as an early noninvasive indicator of allograft injury (2)(3)(4)(5)(6)(7)(8). Among the various strategies to measure dd-cfDNA, we have demonstrated the analytical validity of a targeted next-generation sequencing assay that uses 266 single-nucleotide polymorphisms (SNPs) to accurately quantify dd-cfDNA in the plasma of transplant recipients without the need for genotyping either the donor or the recipient (6).…”

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confidence: 99%

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Biological Variation of Donor-Derived Cell-Free DNA in Renal Transplant Recipients: Clinical Implications

Bromberg

Brennan

Poggio

et al. 2017

The Journal of Applied Laboratory Medicine

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Background Previous studies have demonstrated that donor-derived cell-free DNA (dd-cfDNA) found in circulating blood of transplant recipients may serve as a noninvasive biomarker of allograft rejection. To better interpret the clinical meaning of dd-cfDNA, it is essential to understand the biological variation of this biomarker in stable healthy recipients. This report establishes the biological variation and clinical reference intervals of dd-cfDNA in renal transplant recipients by using an analytically validated assay that has a CV of 6.8%. Methods We sampled venous blood at patient surveillance visits (typically at posttransplant months 1–4, 6, 9, and 12) in a 14-center observational study. Patients with stable renal allograft function spanning ≥3 serial visits were selected. We used AlloSure®, a targeted next-generation sequencing-based approach, to measure dd-cfDNA in the plasma and computed the intraindividual CV (CVI) and interindividual CV (CVG), the index of individuality (II), and reference change value (RCV). Results Of 93 patients, 61% were men, 56% were Caucasian, mean age was 49 years, and 63% were deceased donor kidney recipients. Of 380 blood samples, the dd-cfDNA median value was 0.21% (interquartile range 0.12%–0.39%) and the 97.5th percentile was 1.20%. In 18 patients with an average of 4.1 tests, the CVI was 21%, CVG was 37%, II was 0.57, and RCV was 61%. Conclusions In a renal transplant recipient, a dd-cfDNA level above 1.2% is out of range and potentially abnormal. A serial increase of up to 61% in level of dd-cfDNA in a patient may be attributable to biological variation. Clinicaltrials.gov Identifier: NCT02424227

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Biological Variation of Donor-Derived Cell-Free DNA in Renal Transplant Recipients: Clinical Implications

Bromberg

Brennan

Poggio

et al. 2017

The Journal of Applied Laboratory Medicine

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“…Plasma was extracted from whole-blood samples as previously described (11) with sequencing, preprocessing, and analysis of the known microbiome using our existing pipeline (16). The study was approved by the Stanford University Institutional Review Board.…”

Section: Methodsmentioning

confidence: 99%

“…There are roughly an order of magnitude more nonhuman cells than nucleated human cells in the body (18,19); combining this observation with the average genome sizes of a human, bacterium, and virus (Gb, Mb, and kb, respectively) suggests that approximately 1% of DNA by mass in a human is derived from nonhost origins. Previous studies by us and others have shown that indeed approximately 1% of cfDNA sequences appear to be of nonhuman origin, but only a small fraction of these map to existing databases of microbial and viral genomes (16). This suggests that there is a vast diversity of as yet uncharacterized microbial diversity within the human microbiome and that this diversity can be analyzed through "unmappable" sequencing reads.…”

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confidence: 96%

“…It is not only human cells that shed their nucleic acids into the blood: DNA from plant-based foods has been detected (15), and other life forms such as viruses, bacteria, and fungi release their DNA and RNA into the blood, a phenomenon which has been exploited to determine the presence of infectious disease (12,16) and to measure alterations of the virome due to pharmacological immunosuppression (17). There are roughly an order of magnitude more nonhuman cells than nucleated human cells in the body (18,19); combining this observation with the average genome sizes of a human, bacterium, and virus (Gb, Mb, and kb, respectively) suggests that approximately 1% of DNA by mass in a human is derived from nonhost origins.…”

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confidence: 99%

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Numerous uncharacterized and highly divergent microbes which colonize humans are revealed by circulating cell-free DNA

Kowarsky

Camunas-Soler

Kertesz

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

156

141

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Blood circulates throughout the human body and contains molecules drawn from virtually every tissue, including the microbes and viruses which colonize the body. Through massive shotgun sequencing of circulating cell-free DNA from the blood, we identified hundreds of new bacteria and viruses which represent previously unidentified members of the human microbiome. Analyzing cumulative sequence data from 1,351 blood samples collected from 188 patients enabled us to assemble 7,190 contiguous regions (contigs) larger than 1 kbp, of which 3,761 are novel with little or no sequence homology in any existing databases. The vast majority of these novel contigs possess coding sequences, and we have validated their existence both by finding their presence in independent experiments and by performing direct PCR amplification. When their nearest neighbors are located in the tree of life, many of the organisms represent entirely novel taxa, showing that microbial diversity within the human body is substantially broader than previously appreciated.

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B cell-derived cfDNA after primary BNT162b2 mRNA vaccination anticipates memory B cells and SARS-CoV-2 neutralizing antibodies

Fox-Fisher¹,

Piyanzin²,

Briller

et al. 2022

Med

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Non-Invasive Monitoring of Infection and Rejection After Lung Transplantation

Cited by 7 publications

References 22 publications

Biological Variation of Donor-Derived Cell-Free DNA in Renal Transplant Recipients: Clinical Implications

Biological Variation of Donor-Derived Cell-Free DNA in Renal Transplant Recipients: Clinical Implications

Numerous uncharacterized and highly divergent microbes which colonize humans are revealed by circulating cell-free DNA

B cell-derived cfDNA after primary BNT162b2 mRNA vaccination anticipates memory B cells and SARS-CoV-2 neutralizing antibodies

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