Date: Tuesday, May 2, 2017
Session Name: Poster Session D: Liver: Immunosuppression and Rejection
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall D1
Background: Maintenance immunosuppression after liver transplantation with tacrolimus (TAC) may have progressive fibrosis on serial allograft biopsies. mTOR inhibitors such as rapamycin (RAPA) may abrogate fibrosis. We assessed levels of pro-fibrotic Th2 cytokines in the plasma of patients on maintenance immunosuppression with RAPA versus those on TAC.
Methods: We collected whole blood on pediatric liver transplant patients undergoing routine, annual evaluation in our program from April 2016 to November 2016. Eighteen patient samples were collected and analyzed (TAC = 12, RAPA = 6). Plasma was separated from fresh whole blood samples and Cytometric Bead Array for human Th2 cytokines (Biolegend, San Diego, CA) was performed. Statistical analysis was performed using unpaired student t-test and ANOVA. Patients had no evidence of recent illness or changes in immunosuppression in the prior 3 months. All had histologic absence of rejection.
Results: Mean levels of IL-4, IL-5, IL-6, IL-10 and IL-13 were reduced in RAPA patients compared to patients on TAC (figure 1A) though this did not reach significance (IL-4: 3125 pg/mL (TAC) vs 96 pg/mL (RAPA); IL-5: 4037 vs 41; IL-6: 2173 vs 69; IL-10: 2607 vs 48; IL-13: 1975 vs 165). Plasma levels of TNF-alpha were also reduced in RAPA patients, but not significantly (7957 pg/mL (TAC) vs 1236 pg/mL (RAPA)). The ratio of levels of TNF-alpha to other Th2 cytokine levels was larger for RAPA patients (significantly so for IL-10), suggesting a degree of Th1 skewing (figure 1B). Conclusion: In our small pilot study, we found that mean plasma Th2 cytokine levels[mdash]including hepatic fibrosis-associated IL-4 and IL-13[mdash]are reduced in patients on RAPA compared to those on TAC. This may help to explain improvements in allograft fibrosis in patients on RAPA. More patients will need to be examined to see if these trends are durable.
CITATION INFORMATION: Fischer R, Seng A, Gardner L, Steele L, Harvey L, Wasserkrug H, Andrews W, Hendrickson R, Daniel J, Yankee T. Rapamycin Maintenance Therapy in Pediatric Liver Transplant Recipients Associated with Trend Toward Decreasing Th2 Cytokine Levels Compared to Tacrolimus Therapy. Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:Fischer R, Seng A, Gardner L, Steele L, Harvey L, Wasserkrug H, Andrews W, Hendrickson R, Daniel J, Yankee T. Rapamycin Maintenance Therapy in Pediatric Liver Transplant Recipients Associated with Trend Toward Decreasing Th2 Cytokine Levels Compared to Tacrolimus Therapy. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/rapamycin-maintenance-therapy-in-pediatric-liver-transplant-recipients-associated-with-trend-toward-decreasing-th2-cytokine-levels-compared-to-tacrolimus-therapy/. Accessed December 6, 2019.
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