Detection of donor cell-free dna using digital PCR in lung transplant recipients with graft rejection and infection

2015 ◽  
Vol 76 ◽  
pp. 68 ◽  
Author(s):  
Jun Zou ◽  
Brian Duffy ◽  
Nancy Steward ◽  
Ramsey Hachem ◽  
Thalachallour Mohanakumar
2017 ◽  
Vol 78 (4) ◽  
pp. 342-349 ◽  
Author(s):  
Jun Zou ◽  
Brian Duffy ◽  
Michael Slade ◽  
Andrew Lee Young ◽  
Nancy Steward ◽  
...  

2021 ◽  
Vol 40 (4) ◽  
pp. S320-S321
Author(s):  
J.B. Smith ◽  
J. Stumph ◽  
Y. Bryan ◽  
R. Peterson ◽  
M.P. Steele ◽  
...  

2021 ◽  
Vol 40 (4) ◽  
pp. S338-S339
Author(s):  
M.B. Keller ◽  
C. Mutebi ◽  
P. Shah ◽  
D. Levine ◽  
S. Aryal ◽  
...  

2020 ◽  
Vol 9 (7) ◽  
pp. 2307
Author(s):  
Yan Y. Sanders

The main challenge for a positive long-term outcome in lung transplantation is the lack of early detection for chronic lung allograft dysfunction (CLAD). With advancements in technology, an increasing number of studies demonstrate that cell-free DNA (cfDNA) in body fluids could be used as a marker for disease diagnosis, prognosis or monitoring response to treatment. A previous report from this journal found the joint assessment of cfDNA and CXCL10 from brochoalveolar lavage (BAL) could determine the subphenotypes of CLAD and predict lung transplant survival. This is an exciting attempt in monitoring the progress for lung transplant recipients. More studies and better understanding of cfDNA are needed to develop an accessible and reliable biomarker to monitor the progress of CLAD to improve the long-term survival for lung transplant recipients.


2015 ◽  
Author(s):  
Philip Burnham ◽  
Min Seong Kim ◽  
Sean Agbor-Enoh ◽  
Helen Luikart ◽  
Hannah A Valantine ◽  
...  

Circulating cell-free DNA (cfDNA) is emerging as a powerful monitoring tool in cancer, pregnancy and organ transplantation. Nucleosomal DNA, the predominant form of cfDNA in blood, can be readily adapted for sequencing via ligation of double-stranded DNA (dsDNA) adapters. dsDNA library preparation, however, is insensitive to ultrashort, degraded and single-stranded cfDNA. Drawing inspiration from recent technical advances in ancient genome analyses, we have applied a single-stranded DNA (ssDNA) library preparation method to sequencing of cfDNA in the plasma of lung transplant recipients (40 samples, six patients). We found that the ssDNA library preparation yields a greater portion of sub-100 bp DNA, as well as an increased relative abundance of human mitochondrial cfDNA (10.7x) and microbial cfDNA (71.3x). We report the fragmentation pattern of mitochondrial, nuclear genomic and microbial cfDNA over a broad fragment length range. We furthermore report the first observation of donor-specific mitochondrial cfDNA in the circulation of lung transplant recipients. We found that donor-specific mitochondrial cfDNA molecules are significantly shorter than those specific to the recipient. The higher yield of viral, microbial and fungal sequences that result from the single-stranded ligation approach reduces the cost and increase the sensitivity of cfDNA-based monitoring for infectious complications after transplantation. An ssDNA library preparation method provides a more informative window into understudied forms of cfDNA, including mitochondrial and microbial derived cfDNA and short fragment nuclear genomic cfDNA, while retaining information provided by standard dsDNA library preparation methods.


2020 ◽  
Vol 30 (2) ◽  
pp. 111-116
Author(s):  
Shimon Izhakian ◽  
Walter G. Wasser ◽  
Baruch Vainshelboim ◽  
Avraham Unterman ◽  
Moshe Heching ◽  
...  

Background: Leukocytosis (white blood cell count >12 000/µL) in the delayed postoperative period (4-7 days) after lung transplantation is due to diverse etiologies. We aimed to describe the etiologies of delayed postoperative leukocytosis in lung transplant recipients and to evaluate the association of leukocytosis causes with short-term survival. Methods: A retrospective chart review of 274 lung transplantations performed in our institution during 2006 to 2013. Results: Delayed postoperative leukocytosis was seen in 159 (58.0%) of lung transplant recipients. In 57 (35.8%) of them, the etiology of the leukocytosis was not identified. The etiologies of leukocytosis that were identified were infection (n = 39), second surgery, acute rejection (n = 12), primary graft dysfunction (n = 3), multiple etiologies (n = 17), and other causes (n = 10). On multivariate analysis, delayed postoperative leukocytosis was one of the variables that most significantly associated with decreased survival in the entire sample (hazard ratio [HR] = 1.52, 95% confidence interval [CI]: 1.01-2.29, P = .040). On additional analysis for mortality assessing each leukocytosis subgroup, the data were acute graft rejection (HR = 8.21, 95% CI: 4.09-16.49, P < .001), second surgery (HR = 2.05, 95% CI: 1.08-3.90, P = .020), primary graft dysfunction (HR = 2.72, 95% CI: 0.65-11.33, P = .169), other causes (HR = 1.30, 95% CI: 0.47-3.62, P = .620), and unknown etiology (HR = 0.94, 95% CI: 0.54-1.62, P = .800). Conclusions: Delayed post-lung transplant leukocytosis is a poor prognostic sign, especially when attributed to acute graft rejection, infection, and multiple etiologies. In the absence of an identifiable etiology, it can be attributed to postoperative reactive stress, is not associated with increased mortality, and likely does not warrant further diagnostic investigation.


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