Table 2.

Human translational studies exploring the pathogenesis of PGD

Pathway	Human translational studies	Reference
Epithelial cell injury	Higher blood and BAL levels of RAGE were associated with PGD	(20-22)
	Preexisting or de novo antibodies against type V collagen were associated with lower P/F ratio and PGD	(23, 24)
	Elevated levels of CC16 were associated with higher odds of PGD	(25)
	Higher donor levels of HMGB1 correlated with lower P/F before and after transplantation.	(26)
Endothelial dysfunction	Grade 3 PGD was associated with higher VEGF levels than lower grades of PGD	(27, 28)
	Increased pretransplant endothelin-1 levels were associated with PGD	(29)
	Angiopoietin-2 levels were elevated in PGD	(30)
Chemotaxis and cytokines	Higher plasma levels of MCP-1, IP-10, and IL-2R were associated with PGD	(31)
	Elevated serum IL-8 levels were associated with PGD	(32, 33)
	Higher blood and BAL levels of IL-6 were associated with grade 3 PGD	(34)
Innate immunity	Upregulation in the expression of genes involved in inflammasome and TLR pathways were found in BAL of patients with grade 3 PGD	(35)
	TLR4 mutations associated with innate immune hyporesponsiveness were associated with a lower PGD risk	(36)
	Higher plasma PTX3 levels were seen in those with grade 3 PGD	(37)
	Single nucleotide polymorphisms associated with higher levels of PTX3 were associated with grade 3 PGD	(38)
	Innate lymphoid cells were isolated from BAL of lung transplant recipients	(39)

Adapted from Reference(19)

BAL, bronchoalveolar lavage; CC16, plasma clara cell secretory protein; ET-1, endothelin-1; HMGB1, high-mobility group box-1; IP-10, interferon-inducible protein; MCP-1, monocyte chemotactic protein-1; P/F, PaO₂/FiO₂; PAI-1, plasminogen activator inhibitor-1; PGD, primary graft dysfunction; PTX3, long pentraxin-3; RAGE, receptor for advanced glycation end products; TLR, toll-like receptor; VEGF, vascular endothelial growth factor