BACKGROUND: We previously developed molecular assessment systems for lung transplant transbronchial biopsies (TBBs) with high surfactant and bronchial mucosal biopsies, identifying T-cell‒mediated rejection (TCMR) on the basis of the expression of rejection-associated transcripts, but the relationship of rejection to graft loss is unknown. This study aimed to develop molecular assessments for TBBs and mucosal biopsies and to establish the impact of molecular TCMR on graft survival. METHODS: We used microarrays and machine learning to assign TCMR scores to an expanded cohort of 457 TBBs (367 high surfactant plus 90 low surfactant) and 314 mucosal biopsies. We tested the score agreement between TBB-TBB, mucosal-mucosal, and TBB-mucosal biopsy pairs in the same patient. We also assessed the association of molecular TCMR scores with graft loss (death or retransplantation) and compared it with the prognostic associations for histology and donor-specific antibodies. RESULTS: The molecular TCMR scores assigned in all the TBBs performed similarly to those in high-surfactant TBBs, indicating that variation in alveolation in TBBs does not prevent the detection of TCMR. Mucosal biopsy pieces showed less piece-to-piece variation than TBBs. TCMR scores in TBBs agreed with those in mucosal biopsies. In both TBBs and mucosal biopsies, molecular TCMR was associated with graft loss, whereas histologic rejection and donor-specific antibodies were not. CONCLUSIONS: Molecular TCMR can be detected in TBBs regardless of surfactant and in mucosal biopsies, which show less variability in the sampled tissue than TBBs. On the basis of these findings, molecular TCMR appears to be an important predictor of the risk of future graft failure. TRIAL REGISTRATION: ClinicalTrials.gov NCT02812290.

3rd Department of Surgery University Hospital Motol Prague Czech Republic

Department of Medicine University of Alberta Edmonton Alberta Canada

Department of Surgery Washington University School of Medicine St Louis Missouri

Department of Thoracic Surgery and Transplantation Pomeranian Medical University Szczecin Poland

Department of Thoracic Surgery Medical University of Vienna Vienna Austria

Division of Pulmonary and Critical Care Department of Medicine University of Maryland Baltimore Maryland

Division of Pulmonary and Critical Care Medicine

Lung Transplant Service Alfred Hospital Monash University Melbourne Australia

Pulmonary Disease and Critical Care Medicine University of Texas San Antonio San Antonio Texas

Toronto Lung Transplant Program University of Toronto Toronto Ontario Canada

J Heart Lung Transplant. 2020 Dec;39(12):1338-1340. doi: 10.1016/j.healun.2020.09.007. PubMed

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ClinicalTrials.gov
NCT02812290