Session Time: 4:30pm-6:00pm
Presentation Time: 5:42pm-5:54pm
Location: Room 3AB
Background: Previously we reported a novel biomarker gene set for the identification of tolerance in murine models of rapamycin-induced cardiac tolerance and spontaneous hepatic tolerance. GeXP multiplex rRT-PCR was used to amplify 22 prominent immunoregulatory genes, in cardiac and liver grafts, which were then correlated with the pathological and biochemical parameters of transplanted organs. Subsequently, an 8 gene expression panel, consisting of the increased expression of 6 immunoregulatory genes and the decreased expression of 2 pro-inflammatory genes, was found to be predictive of tolerance.
Methods:In this Phase 2A single center study (LITMUS), we examined whether an 8 target and 5 housekeeping gene expression panel in the peripheral blood mononuclear cells (PBMC) and liver allograft could identify operationally tolerant liver transplant recipients. We first measured the panel in PBMC from 54 adult liver transplant recipients who were a minimum of 3 months post-transplant and who had no biochemical evidence of rejection. Patients with a putative tolerant gene profile in PBMC had a liver biopsy and were then weaned off immunosuppression to confirm that the gene profile identified a tolerant state.
Results: Of the 54 patients studied, 16 had the putative tolerance gene profile in their PBMC. Age, gender, indication for transplant, and CNI choice did not correlate with having the tolerant profile. Twelve patients agreed to enter the withdrawal phase of the study. Prior to withdrawal, a liver biopsy was performed, and 2 patients were excluded as their biopsies showed recurrent autoimmune disease and rejection. Of the 10 remaining patients 5 have now been weaned off of immunosuppresion (IS), 2 are undergoing withdrawal and 3 developed acute cellular rejection, which was easily reversed. Five of eight patients who had the gene expression profile both in liver and PBMC were successfully weaned off IS.
Conclusion: These data suggest that a combination of gene expression monitoring in PBMC and liver allograft may identify operationally tolerant recipients.
CITATION INFORMATION: Chruscinski A., Rojas-Luengas V., Issacher A., Luo J., Yowanto H., Selzner N., Lilly L., Smith R., Renner E., Zhang J., Grant D., Adeyi O., Atkins H., Juni P., Levy G. Results of LITMUS (NCT 02541916): The Liver Immune Tolerance Bio Marker Utilization Study Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:Chruscinski A, Rojas-Luengas V, Issacher A, Luo J, Yowanto H, Selzner N, Lilly L, Smith R, Renner E, Zhang J, Grant D, Adeyi O, Atkins H, Juni P, Levy G. Results of LITMUS (NCT 02541916): The Liver Immune Tolerance Bio Marker Utilization Study [abstract]. https://atcmeetingabstracts.com/abstract/results-of-litmus-nct-02541916-the-liver-immune-tolerance-bio-marker-utilization-study/. Accessed July 30, 2021.
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