Molecular Immunity Unit, University of Cambridge, Department of Medicine, Cambridge, UK.
Institute of Transplantation, Freeman Hospital, Newcastle Upon Tyne, UK.
Clin Transplant. 2022 Apr;36(4):e14570. doi: 10.1111/ctr.14570. Epub 2022 Jan 10.
Transplantation is an effective treatment for end-stage lung disease, but the donor organ shortage is a major problem. Ex-vivo lung perfusion (EVLP) of extended criteria organs enables functional assessment to facilitate clinical decision-making around utilization, but the molecular processes occurring during EVLP, and how they differ between more or less viable lungs, remain to be determined.
We used RNA sequencing of lung tissue to delineate changes in gene expression occurring in 10 donor lungs undergoing EVLP and compare lungs that were deemed non-transplantable (n = 4) to those deemed transplantable (n = 6) following perfusion.
We found that lungs deemed unsuitable for transplantation had increased induction of innate immune pathways and lower expression of oxidative phosphorylation related genes. Furthermore, the expression of SCGB1A1, a gene encoding an anti-inflammatory secretoglobin CC10, and other club cell genes was significantly decreased in non-transplantable lungs, while CHIT-1 was increased. Using a larger validation cohort (n = 17), we confirmed that the ratio of CHIT1 and SCGB1A1 protein levels in lung perfusate have potential utility to distinguish transplantable from non-transplantable lungs (AUC .81).
Together, our data identify novel biomarkers that may assist with pre-transplant lung assessment, as well as pathways that may be amenable to therapeutic intervention during EVLPAQ6.
移植是治疗终末期肺病的有效方法，但供体器官短缺是一个主要问题。扩展标准器官的体外肺灌注 (EVLP) 使功能评估成为可能，从而有助于围绕利用进行临床决策，但 EVLP 过程中发生的分子过程以及它们在更有活力或活力较低的肺之间的差异仍有待确定。
我们使用肺组织的 RNA 测序来描绘在 10 个接受 EVLP 的供体肺中发生的基因表达变化，并比较灌注后被认为不适合移植的肺（n=4）和适合移植的肺（n=6）。
我们发现，被认为不适合移植的肺中先天免疫途径的诱导增加，氧化磷酸化相关基因的表达降低。此外，非移植肺中 SCGB1A1（编码抗炎分泌球蛋白 CC10 的基因）和其他俱乐部细胞基因的表达显著降低，而 CHIT-1 增加。使用更大的验证队列（n=17），我们证实肺灌洗液中 CHIT1 和 SCGB1A1 蛋白水平的比值具有区分可移植和不可移植肺的潜在用途（AUC.81）。
总之，我们的数据确定了新的生物标志物，这些标志物可能有助于移植前的肺评估，以及在 EVLPAQ6 期间可能适合治疗干预的途径。
