GSE262742 Redefining the molecular rejection states in 3230 heart transplant biopsies: relationships to parenchymal injury and graft survival

Contributor : Jessica ChangSeries Type : Expression profiling by arrayOrganism : Homo sapiensThe first-generation Molecular Microscope ® (MMDx) system for heart transplant endomyocardial biopsies used expression of rejection-associated transcripts (RATs) to diagnose T cell-mediated rejection (TCMR) and antibody-mediated rejection (ABMR) but also detected acute injury. However, the ideal system should detect rejection without being influenced by injury, to permit analysis of the relationship between rejection and parenchymal injury. To achieve this, we developed a new rejection classification in an expanded cohort of 3230 biopsies: 1641 from INTERHEART (ClinicalTrials.gov #NCT02670408), plus 1589 service biopsies added to imp rove the power of the machine learning algorithms. The new system used six rejection classifiers instead of RATs and generated seven rejection archetypes: No Rejection 48%; Minor 24%; TCMR1 2.3%; TCMR2 2.7%; TCMR/Mixed 2.7%; EABMR 3.9%; and FABMR 16%. Using rejection classifiers eliminated cross-rea ctions with acute injury, permitting separate assessment of rejection and injury. TCMR was associated with severe recent injury and late atrophy-fibrosis and rarely had normal parenchyma. ABMR was better tolerated, seldom producing severe injury, but in later biopsies was often associated with atrop hy-fibrosis, indicating long term risk. Graft survival and LVEF were reduced in hearts with TCMR, but also in hearts with severe-recent injury and atrophy-fibro...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by array Homo sapiens Source Type: research