The role of predictive biomarkers during clinical ex vivo lung perfusion

Objective identification during ex-vivo lung perfusion (EVLP) of which donor lungs can be successfully transplanted or reconditioned during ex-vivo lung perfusion (EVLP) has driven the search for reliable predictive biomarkers. A couple of new publications from both sides of the Atlantic have recently reported important progress on this front.

During 100 sequential EVLP procedures, Hashimoto et al screened a series of protein biomarkers related to epithelial cell death and inflammation for their ability to predict primary graft dysfunction (PGD) and clinical outcomes. Levels of two of these, (M30 and HMGB-1) measured by ELISA assays in the EVLP perfusate were shown to correlate with PGD after lung transplantation in samples taken over 1 to 4 hours after the start of EVLP. Higher levels of M30 and HMGB-1 were also associated with higher mortality in Cox regression.

And as part of the European DEVELOP-UK study first presented as an abstract last year and now as a full publication in JHLT, Andreasson et al assessed the predictive value of markers of inflammation and tissue injury in 42 donor lungs undergoing EVLP.

The most effective markers to differentiate between in-hospital survival and non-survival post-transplant were perfusate interleukin (IL)-1β (p = 0.002) and tumor necrosis factor-α (p = 0.006) after 30 minutes of EVLP. Interestingly, both these biomarkers can nowadays be rapidly detected by a new rapid cytokine assay, using microfluidics which yields “point of care” results within 30 -45 mins during EVLP. (These assays previously took 24 -48 hours!)

The authors add “Blocking the IL-1β pathway during EVLP may reduce endothelial activation and subsequent neutrophil adhesion on reperfusion.”

And on a related topic, a small pilot study from Brussels (Belhaj et al) suggests that reduced gene expression of donor lung surfactants A and B prior to implantation are associated with increased incidence of lung infiltrates after transplantation.

References:

5. Hashimoto K et al, Higher M30 and high mobility group box 1 protein levels in ex vivo lung perfusate are associated with primary graft dysfunction after human lung transplantation. J Heart Lung Transplant. 2017 Jun 21. pii: S1053-2498(17)31870-3] (link to abstract)
6. Andreassson A et al, The role of interleukin-1β as a predictive biomarker and potential therapeutic target during clinical ex vivo lung perfusion. JHLT Sept 2017 Vol 36, Issue 9, Pages 985–995] (link to abstract)
7. Belhaj A et al, Influence of Donor Lung Surfactant-A and -B Protein Expression on the Development of Primary Graft Dysfunction After Lung Transplantation: A Pilot Study. Ann Transplant. 2017 Jun 16;22:361-369.] (link to abstract)

Xvivo Insights PB-2017-11-28