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Noninvasive monitoring of infection and rejection after lung transplantation.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2015 Oct 27; Vol. 112 (43), pp. 13336-41. Date of Electronic Publication: 2015 Oct 12. - Publication Year :
- 2015
-
Abstract
- The survival rate following lung transplantation is among the lowest of all solid-organ transplants, and current diagnostic tests often fail to distinguish between infection and rejection, the two primary posttransplant clinical complications. We describe a diagnostic assay that simultaneously monitors for rejection and infection in lung transplant recipients by sequencing of cell-free DNA (cfDNA) in plasma. We determined that the levels of donor-derived cfDNA directly correlate with the results of invasive tests of rejection (area under the curve 0.9). We also analyzed the nonhuman cfDNA as a hypothesis-free approach to test for infections. Cytomegalovirus is most frequently assayed clinically, and the levels of CMV-derived sequences in cfDNA are consistent with clinical results. We furthermore show that hypothesis-free monitoring for pathogens using cfDNA reveals undiagnosed cases of infection, and that certain infectious pathogens such as human herpesvirus (HHV) 6, HHV-7, and adenovirus, which are not often tested clinically, occur with high frequency in this cohort.
- Subjects :
- Base Sequence
Cytomegalovirus genetics
Humans
Molecular Sequence Data
Polymorphism, Single Nucleotide genetics
Sequence Analysis, DNA
Species Specificity
Surgical Wound Infection virology
DNA, Viral blood
Graft Rejection diagnosis
Lung Transplantation adverse effects
Postoperative Care methods
Surgical Wound Infection diagnosis
Subjects
Details
- Language :
- English
- ISSN :
- 1091-6490
- Volume :
- 112
- Issue :
- 43
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 26460048
- Full Text :
- https://doi.org/10.1073/pnas.1517494112