In vitro lymphocyte culture-based allo-specific cytokine response profiles predictive of acute rejection in kidney allografts

Abstract

Background: In vitro allo-specific cytokine response to prospective allograft antigens might provide a means to identify patients at risk to adverse clinical endpoints/graft failure and predict allograft survival after transplantation. Methods: Cytokine profiles of recipient's peripheral blood mononuclear cells cocultured with allograft antigen-pulsed recipient macrophages were studied in 49 renal transplant recipients, 19 of which has acute rejection-12 with acute cellular rejection (ACR) and 37 non-ACR allografts. Cytometric bead array was used to analyze 18 cytokines/chemokines in the culture supernatants of graft antigen-pulsed and un-pulsed cultures. The mean increment in cytokine expression in stimulated versus unstimulated cultures was calculated. Results: Interleukin 6 (IL-6) (2336.42 ± 213.4 vs. 1244.06 ± 224 fg/ml; P = 0.0070), IL-1α (28.3 ± 7.451 vs. 16.78 ± 5.513 fg/ml; P = 0.0417), IL-17A (201 ± 96.73 vs. 28.91 ± 18.45 fg/ml; P = 0.0262), and MIP-1α/CCL3 (2682.25 ± 1013 vs. 1748.99 ± 780.4 pg/ml; P = 0.0383) were found to be high in rejection compared to stable allografts. Similarly, IL-6, IP-10/CXCL10, MIP-1α, and MCP-1 were increased in ACR, whereas granzyme B (11.36 ± 7.974 vs. 28.71 ± 9.393 pg/ml; P = 0.0011) and RANTES/CCL5 were higher in the non-ACR group. Conclusion: Distinct allo-specific in vitro cytokine profiles correlated with the occurrence of posttransplantation rejection episodes in the cohort, which indicated the feasibility of this in vitro model to predict transplant outcomes.

Keywords

• acute rejection
• cytokines
• in vitro culture model
• kidney transplant