Association of donor single-cell cytokine secretion & circulating cytokine levels with the development & trajectory of severe primary graft dysfunction in lung transplantation.

Abstract

Whether donor immune biology at procurement is associated with primary graft dysfunction (PGD) trajectory is unknown. Pre-transplant donor T-cell function and circulating plasma proteins were profiled to address this gap. Twenty-one recipients were classified as no PGD (NOGD, n=7), recovery after initial PGD3 (RECV, n=5), or sustained PGD3 (SGD, n=9). The polyfunctionality of T-cells isolated from donor peripheral blood mononuclear cell (PBMC) after stimulation and plasma levels of 92 proteins were assessed. CD8+ polyfunctionality strength index (PSI) was lowest in RECV (p=0.019), driven by effector and chemoattractive clusters. CD4+ did not differ. SGD showed higher secretion of several proinflammatory mediators, while NOGD had higher TGF-β1 secretion and circulating CD27, and lower IFN-γ. SGD had the lowest circulating HGF and PDGF-B, while RECV had higher PDCD1, IL-33, HGF, and LAMP3. Donor T-cell polyfunctionality and circulating biomarkers correlated with PGD3 trajectory, with RECV associated with an exhausted and anti-inflammatory donor phenotype.