Journal Article

Noninvasive monitoring of infection and rejection after lung transplantation

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

2015

Overview

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 post-transplant 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.

• Publisher: National Academy of Sciences,National Acad Sciences
• Subject: Base Sequence / Biological Sciences / Cytomegalovirus / Cytomegalovirus - genetics / Deoxyribonucleic acid / DNA / DNA, Viral - blood / Graft Rejection - diagnosis / Humans / Lung Transplantation - adverse effects / Molecular Sequence Data / Pathogens / Polymorphism, Single Nucleotide - genetics / Postoperative Care - methods / Sequence Analysis, DNA / Species Specificity / Surgical Wound Infection - diagnosis / Surgical Wound Infection - virology / Survival / Transplants & implants