Molecular features of DSA-negative ABMR in heart transplants are nearly identical to DSA-positive ABMR, with both showing high dd-cfDNA positivity.
Are there molecular and dd-cfDNA differences between DSA-negative and DSA-positive antibody-mediated rejection in heart transplant recipients?
DSA-negative and DSA-positive molecular antibody-mediated rejection in heart transplants share virtually identical molecular features and high dd-cfDNA levels, suggesting similar underlying mechanisms likely involving NK cells.
Absolute Event Rate: 0% vs 0%
AbstractBackground Antibody-mediated rejection (ABMR) in heart transplants is often negative for donor-specific antibody (DSA). We explored potential molecular differences between DSA-negative and DSA-positive molecular ABMR in 212 heart endomyocardial biopsies (EMBs) from the prospective Trifecta-Heart study (NCT04707872). Methods We characterized rejection in biopsies by the Molecular Microscope® Diagnostic System (MMDx) and by histology, and at time of biopsy measured donor-derived cell-free DNA (dd-cfDNA, the Prospera™ test, Natera, Inc.) and central plasma DSA (One Lambda Inc., assessed by LGH). Results MMDx ABMR was 53% (33/63) DSA-positive and 79% (50/63) dd-cfDNA positive. DSA-negative (N=33) and DSA-positive (N=30) molecular ABMR were similar in days posttransplant (861 vs 1119), %dd-cfDNA positivity (76% vs 83%), and mean LVEF (58.5 vs 56.5); DSA-negative ABMR had lower molecular ABMR activity (ABMRProb score 0.55 vs 0.70, P=0.02). Gene expression profiles were essentially identical between DSA-negative and DSA-positive molecular ABMR, including IFNG-inducible genes (e.g. CXCL11, CXCL9, IDO1) and NK-expressed genes (e.g. KLRD1, GNLY), compatible with a role for NK cells in both DSA-negative and DSA-positive ABMR. Conclusions Molecular features of heart transplant biopsies with DSA-negative ABMR are virtually identical to those with DSA-positive ABMR and both are associated with high plasma dd-cfDNA.
Madill-Thomsen et al. (Sun,) reported a other. Molecular features of DSA-negative ABMR in heart transplants are nearly identical to DSA-positive ABMR, with both showing high dd-cfDNA positivity.