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. Author manuscript; available in PMC: 2019 Mar 1.

Published in final edited form as: Transplantation. 2018 Mar;102(3):e90–e100. doi: 10.1097/TP.0000000000002044

Intra-graft gene expression profiling in naive monkey heart (Normal, n=4), untreated allografts (No Rx, n=5), or allografts from recipients treated with sc28AT (blue, n=4), hu5C8 (green, n=4) or sc28AT+hu5C8 (red, n=5). (A) Heat-map analysis for the entire custom panel of 60 genes. Each column represents 1 allograft tissue specimen. Hu5C8±sc28AT-treated groups were analyzed both during therapy (d14–28 posttransplant) and around the time of hu5C8-therapy withdrawal (d75–150). The rectangular box with red contours in the centre delineates a cluster of genes that tend to be expressed at lower levels in protocol biopsies collected under combined drug treatment (d14–28) than in either monotherapy groups at the same time, and more similar to nontransplanted monkey heart tissue (Normal). Arrows denote 6 most differentially expressed or pathway relevant genes shown in more details in panel B. Results represent the mean ± SEM of normalized counts for each group. (B) During the first month after transplantation, sc28AT is associated with significantly increased expression of GZMB, IFNG, IL-6, IDO1, PDL-2, and PD-1, and MARCKS and CTLA-4 (not illustrated) compared to sc28AT+hu5C8. Expression of ICOS and Foxp3 was increased in rejecting (untreated and sc28AT-treated) allografts and in grafts protected by either hu5C8 alone or sc28AT+hu5C8. Asterisks denote p values < 0.05 between groups for the indicated comparisons, determined using the NanoString nSolver® Analysis Software.

Intra-graft gene expression profiling in naive monkey heart (Normal, n=4), untreated allografts (No Rx, n=5), or allografts from recipients treated with sc28AT (blue, n=4), hu5C8 (green, n=4) or sc28AT+hu5C8 (red, n=5). (A) Heat-map analysis for the entire custom panel of 60 genes. Each column represents 1 allograft tissue specimen. Hu5C8±sc28AT-treated groups were analyzed both during therapy (d14–28 posttransplant) and around the time of hu5C8-therapy withdrawal (d75–150). The rectangular box with red contours in the centre delineates a cluster of genes that tend to be expressed at lower levels in protocol biopsies collected under combined drug treatment (d14–28) than in either monotherapy groups at the same time, and more similar to nontransplanted monkey heart tissue (Normal). Arrows denote 6 most differentially expressed or pathway relevant genes shown in more details in panel B. Results represent the mean ± SEM of normalized counts for each group. (B) During the first month after transplantation, sc28AT is associated with significantly increased expression of GZMB, IFNG, IL-6, IDO1, PDL-2, and PD-1, and MARCKS and CTLA-4 (not illustrated) compared to sc28AT+hu5C8. Expression of ICOS and Foxp3 was increased in rejecting (untreated and sc28AT-treated) allografts and in grafts protected by either hu5C8 alone or sc28AT+hu5C8. Asterisks denote p values < 0.05 between groups for the indicated comparisons, determined using the NanoString nSolver® Analysis Software.