Enhanced AMR detection using the Molecular Microscope Diagnostic System following heart transplantation

A prospective, single-center diagnostic study, evaluating the impact of donor-specific antibodies (DSA) and donor-derived cell-free DNA (dd-cfDNA) on antibody-mediated rejection (AMR) detection using the Molecular Microscope Diagnostic System (MMDx) in heart transplant recipients, was published in The Journal of Heart and Lung Transplantation by Valledor et al. A total of 351 for-cause endomyocardial biopsies from 223 heart transplant recipients were assessed. Diagnostic performance was evaluated by receiver operating characteristic (ROC) analysis. 

Key data: MMDx identified AMR more frequently than histology overall (14.8% vs 6.0%; odds ratio [OR], 3.26; 95% confidence interval [CI], 1.65–6.45; p = 0.0007), in DSA-positive samples (n = 172; 21.5% vs 10.5%; OR, 3.06; 95% CI, 1.33–7.07; p = 0.009), and in DSA-negative samples (n = 179; 8.4% vs 1.7%; OR, 4.18; 95% CI, 1.48–11.85; p = 0.007). When stratified by antibody strength, MMDx detected AMR with higher odds than histology in low-mean fluorescence intensity (MFI) samples (<4,000 MFI; 19.2% vs 2.6%; OR, 10.80; 95% CI, 2.18–53.42; p = 0.003). For MMDx-defined AMR, dd-cfDNA demonstrated greater discriminatory performance than DSA (ROC area under the curve [AUC], 0.80 vs 0.52; p < 0.001). 

Key learning: These data support the diagnostic utility of adjunctive MMDx analysis in AMR assessment, where it demonstrates higher diagnostic yield than histology, particularly in cases of low-MFI DSA. A combination of molecular and plasma-based diagnostics may enhance multimodal surveillance strategies.