Gene set enrichment analysis identifies key innate immune pathways in primary graft dysfunction after lung transplantation.

摘要: We hypothesized alterations in gene expression could identify important pathways involved transplant lung injury. Broncho alveolar lavage fluid (BALF) was sampled from donors prior to procurement and recipients within an hour of reperfusion as part the NIAID Clinical Trials Organ Transplantation Study. Twenty-three patients with Grade 3 primary graft dysfunction (PGD) were frequency matched controls based on donor age recipient diagnosis. RNA analyzed using Human Gene 1.0 ST array. Normalized mRNA transformed differences between postreperfusion values ranked then tested Set Enrichment Analysis. Three-hundred sixty-two sets upregulated, eight meeting significance (familywise-error rate, FWER p-value <0.05), including NOD-like receptor inflammasome (NLR; p < 0.001), toll-like receptors (TLR; IL-1 (p = myeloid differentiation response 88 NFkB activation by nontypeable Haemophilus influenzae TLR4 0.008) TLR 9 0.018). The top five individual transcripts these rank metric score are predominantly present NLR pathways, IL1β (1.162), NLRP3 (1.135), IL1α (0.952), IL6 (0.931) CCL4 (0.842). set enrichment analyses implicate inflammasome-mediated innate immune signaling key mediators development PGD patients.