Impact of cytomegalovirus infection on gene expression profile in heart transplant recipients

Sparing the Prod: Providing an Alternative to Endomyocardial Biopsies With Noninvasive Surveillance After Heart Transplantation During COVID-19

“…2,3 However, GEP has limitations in that it cannot be used within 55 days of HT, or in the setting of recent high dose immunosuppression as these factors can influence predictive value of GEP testing and these patients were excluded from trials. 3,6,7 GEP may be falsely positive in recipients with active viral infections and should be interpreted with caution in this cohort. 3,6,7 J o u r n a l P r e -p r o o f More recently, donor-derived cell-free DNA (dd-cfDNA) (AlloSure ® , CareDx ® Inc, Brisbane, California) from peripheral blood samples can be safely used to rule out ACR and Antibody Mediated Rejection (AMR) as early as 2 weeks after transplantation and allow for surveillance of rejection in HT recipients.…”

“…3,6,7 GEP may be falsely positive in recipients with active viral infections and should be interpreted with caution in this cohort. 3,6,7 J o u r n a l P r e -p r o o f More recently, donor-derived cell-free DNA (dd-cfDNA) (AlloSure ® , CareDx ® Inc, Brisbane, California) from peripheral blood samples can be safely used to rule out ACR and Antibody Mediated Rejection (AMR) as early as 2 weeks after transplantation and allow for surveillance of rejection in HT recipients. 8 HeartCare ® (CareDx ® Inc, Brisbane, California) provides a comprehensive assessment of graft rejection by combining GEP and dd-cfDNA, where the tests complement each other to provide a more holistic picture of graft health.…”

“… 2 , 3 However, GEP has limitations in that it cannot be used within 55 days of HT, or in the setting of recent high dose immunosuppression as these factors can influence predictive value of GEP testing and these patients were excluded from trials. 3 , 6 , 7 GEP may be falsely positive in recipients with active viral infections and should be interpreted with caution in this cohort. 3 , 6 , 7 …”

“… 3 , 6 , 7 GEP may be falsely positive in recipients with active viral infections and should be interpreted with caution in this cohort. 3 , 6 , 7 …”

The NLRP3 Inflammasome: Relevance in Solid Organ Transplantation

“…Interestingly, homeostatic levels of cfDNA do not promote pathology, however it is hypothesized changes in methylation status, fragment length, and quantity contribute to the pathogenicity and immunogenicity of cfDNA. In solid organ transplantation, elevations in levels of cfDNA specifically derived from the donor allograft (donor-derived cell-free DNA, dd-cfDNA) is associated both directly with allograft injury, as well as serving as a risk stratification factor for poor clinical outcomes across solid organs in adult and pediatric recipients alike [ 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 ]. Perhaps most strikingly, in a multicenter cohort of prospectively recruited patients all of which presented with biopsy-confirmed T cell-mediated rejection of Banff class 1A or borderline rejection, dd-cfDNA scores above 0.5% at any time during surveillance were associated with significantly higher decline in estimated glomerular filtration rate (eGFR, a standard measure of renal allograft function), a nearly 20-fold increase in the rate of de novo donor-specific antibody (DSA) development, and a significant increase in the rate of rejection recurrence or worsening 3–6 months following dd-cfDNA measurement [ 53 ].…”