Immunosuppressive therapy in liver transplantation: strategies for personalization approaches

Abstract

Immunosuppressive therapy in organ transplantation is tentatively moving from a phase of empirical administration towards individualized therapy. This process is highly dependent on the development of monitoring methods to detect individual immune states. Anti-donor alloreactivity, which depends on the number and phenotype of alloreactive precursors in the recipient, could be used to monitor the immune state for individualizing immunosuppressive therapy. For this purpose, we have applied the mixed lymphocyte reaction assay, an assay in which CFSE-labeled PBMCs from recipients are cultured with allogeneic lymphocytes from donors as stimuli, to clinical liver transplantation (LT). This method allows for the separate quantification of the proliferation of CD4 and CD8 responder T cells in response to allo-stimulation by using multiparameter FCM. In addition to the cellular ex vivo assay, analyses by molecular genetics such as the single nucleotide polymorphism (SNP) testing would lead to an improvement in risk prediction, early detection and prevention of various complications after organ transplantation. We have recently demonstrated that Fc-gamma receptor SNPs are predisposing factors for bloodstream infections and can predict mortality after living donor LT. We have also investigated the impact of SNPs in the FOXP3 gene, a master regulator gene of regulatory T cells, on rejection severity in liver transplant recipients. We found that FOXP3 SNP rs3761548 A/C could be a predisposing factor for steroid-resistant acute rejection after liver transplantation. In this talk, I would like to introduce how we practice individualizing immunosuppressive therapy by making use of cellular immunology and molecular genetics in LT.