Peripheral phenotype and gene expression profiles of combined liver-kidney transplant patients

Background and Aims: The beneficial effect of one graft on another has been reported in combined transplantation but the associated mechanisms and biological influence of each graft have not yet been established. Methods: In multiple analyses, we explored the PBMC phenotype and signature of 45 immune-related messenger RNAs and 754 microRNAs from a total of 235 patients, including combined liver-kidney transplant recipients (CLK), patients with a liver (L-STA) or kidney (K-STA) graft only under classical immunosuppression and patients with tolerated liver (L-TOL) or kidney grafts (K-TOL). Results: CLK show an intermediary phenotype with a higher percentage of peripheral CD19⁺CD24⁺CD38^Low memory B cells and Helios⁺ Treg cells, two features associated with tolerance profiles, compared to L-STA and K-STA (P < 0.05, P < 0.01). Very few miRNA were significantly differentially expressed in CLK vs. K-STA and even fewer when compared to L-STA (35 and 8, P < 0.05). Finally, CLK are predicted to share common miRNA targets with K-TOL and even more with L-TOL (344 and 411, P = 0.005). Altogether CLK display an intermediary phenotype and gene profile, which is closer to that of liver transplant patients, with possible similarities with the profiles of tolerant patients. Conclusion: These data suggest that CLK patients show the immunological influence of both allografts with liver having a greater influence.