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Noninvasive monitoring of infection and rejection after lung transplantation.


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.

SUBMITTER: De Vlaminck I 

PROVIDER: S-EPMC4629384 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Noninvasive monitoring of infection and rejection after lung transplantation.

De Vlaminck Iwijn I   Martin Lance L   Kertesz Michael M   Patel Kapil K   Kowarsky Mark M   Strehl Calvin C   Cohen Garrett G   Luikart Helen H   Neff Norma F NF   Okamoto Jennifer J   Nicolls Mark R MR   Cornfield David D   Weill David D   Valantine Hannah H   Khush Kiran K KK   Quake Stephen R SR  

Proceedings of the National Academy of Sciences of the United States of America 20151012 43


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  ...[more]

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