Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
Division of Pulmonary and Critical Care, Department of Medicine, University of Maryland, Baltimore, Maryland.
J Heart Lung Transplant. 2020 Dec;39(12):1327-1337. doi: 10.1016/j.healun.2020.08.013. Epub 2020 Aug 26.
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.
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.
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.
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.
ClinicalTrials.gov NCT02812290.
我们之前开发了一种针对高表面活性剂和支气管黏膜活检的肺移植经支气管活检（TBB）的分子评估系统，根据排斥相关转录本的表达来识别 T 细胞介导的排斥反应（TCMR），但排斥反应与移植物丢失的关系尚不清楚。本研究旨在开发 TBB 和黏膜活检的分子评估，并确定分子 TCMR 对移植物存活的影响。
我们使用微阵列和机器学习为 457 个 TBB（367 个高表面活性剂加 90 个低表面活性剂）和 314 个黏膜活检分配 TCMR 评分。我们测试了同一患者的 TBB-TBB、黏膜-黏膜和 TBB-黏膜活检对之间的评分一致性。我们还评估了分子 TCMR 评分与移植物丢失（死亡或再次移植）的相关性，并将其与组织学和供体特异性抗体的预后相关性进行了比较。
所有 TBB 中的分子 TCMR 评分与高表面活性剂 TBB 中的评分相似，这表明 TBB 中肺泡的变异不会阻止 TCMR 的检测。黏膜活检片的标本间变异小于 TBB。TBB 中的 TCMR 评分与黏膜活检一致。在 TBB 和黏膜活检中，分子 TCMR 与移植物丢失相关，而组织学排斥和供体特异性抗体则不相关。
无论是否有表面活性剂，分子 TCMR 都可以在 TBB 中检测到，而在黏膜活检中，所取样组织的变异性小于 TBB。基于这些发现，分子 TCMR 似乎是未来移植物失败风险的重要预测指标。
ClinicalTrials.gov NCT02812290。
