Follistatin-like 1 and Biomarkers of Neutrophil Activation Are Associated with Poor Short-Term Outcome after Lung Transplantation on VA-ECMO

Abstract

The investigation of biomarkers associated with undesired outcome following lung transplantation (LuTX) is essential for a better understanding of the underlying pathophysiology, an earlier identification of susceptible recipients and the development of targeted therapeutic options. We therefore determined the longitudinal perioperative course of putative cytokines related to neutrophil activation (chemokine CC motif ligand 4 (CCL-4), interleukin (IL)-23 and Lipocalin 2 (LCN2)) and a cytokine that has been implicated in graft-versus-host disease (Follistatin-like 1 (FSTL1)) in 42 consecutive patients undergoing LuTX. We plotted receiver-operating curves (ROC) to assess the predictive power of the measured cytokines for short-term outcomes namely primary graft dysfunction (PGD), early complications requiring extracorporeal membrane oxygenation (ECMO), and a high postoperative sequential organ failure assessment (SOFA). All cytokines increased immediately after surgery. ROC analyses determined significant associations between CCL4 and a high SOFA score (area under the curve (AUC) 0.74 (95%CI:0.5–0.9; p < 0.05), between LCN2 and postoperative ECMO support (AUC 0.73 (95%CI:0.5–0.9; p < 0.05), and between FSTL1 and PGD (AUC 0.70 (95%CI:0.5–0.9; p < 0.05). The serum concentrations of the neutrophil-derived cytokines LCN2 and CCL4 as well as FSTL1 were all related to poor outcome after LuTX. The specific predictive power, however, still has to be assessed in larger trials. The potential role of FSTL1 as a biomarker in the development of PGD could be of great interest particularly since this protein appears to play a crucial role in allograft tolerance.

Early serum biomarkers to characterise different phenotypes of primary graft dysfunction after lung transplantation: a systematic scoping review

“…As per the resulting study cohorts, most studies included single and double LUTX. Only three studies (41,43,52) included only double LUTX. Furthermore, none of the above studies differentiated outcomes or biomarker concentration among single or double LUTX cohorts.…”

“…Various inflammatory mediators were explored as potential biomarkers of PGD. These included acute phase reactants like procalcitonin (PCT) and pentraxin-3 (PTX3), cytokines such as Of the 26 candidate biomarkers identified in this review, only sRAGE, ICAM-1, PA1-1, SP-D and FSTL-1 were evaluated at least once using AUROCC analysis (see Table 2), in 3 different studies (40,41,44) -including 406 unique patients (276 double LUTX). No single test demonstrated a good diagnostic accuracy (AUROCC >0.75), and the reported AUROCC ranged from 0.58 (0.51, 0.65) for ICAM-1, up to 0.73 (0.66, 0.79) for PAI-1, with a median value of 0.58 (0.51, 0,78).…”