Table 2. GSA identifies increasing enrichment of IL-17 gene-sets in human renal allograft acute rejection across independent Patient Data-Sets.
Analysis | Gene-Sets | p-value | FDR | |
Discovery Data-Set (n = 66) | ||||
AR vs. STA | IL17-Pathway | 0.007 | 0.3 | |
Th17 gene set | 0 | 0.2 | ||
D0> STA> BL>ARIA> ARIB | IL17-Pathway | 0.011 | 0.3076 | |
Verification Data-Set (n = 35) | ||||
AR vs. STA | IL17-Pathway | 0.011 | 0.33 | |
Th17 gene set | 0.026 | 0.39 | ||
STA> BL>AR | IL17-Pathway | 0.008 | 0.5 |
There were total 140 gene-sets significantly enriched in AR in both Data-Sets (FDR = 0.5), the IL-17 pathway and Th17 gene-sets are listed above. Other significant gene-sets that reached the threshold of FDR = 0.5 included gene-sets associated with innate immune cells (Dendritic Cell, Natural Killer Cell, Granulocyte, Monocyte), and innate immune responses (CTLA4 pathway, Toll-like receptor pathway, NFKB targets, PD1 signaling), with Cytokine Signaling (IL-10, IL-2, IL-5, IL-22BP, IL-12) as well as with gene-sets related to Th-differentiation and activation (CD40 signaling, Costimulation, Th1/Th2, Th-Differentiation). Th1 (FDR = 0.3, p = 0.007) and IL-12 (FDR = 0.3, p = 0.011) had higher FDR and p-values compared to the Th17 and IL-17 gene-sets in our data-set and similar values compared to GSE 9493. Other gene-sets were Graft versus Host Disease, Autoimmune Thyroiditis, and Antigen processing.