T cell activation marker HLA-DR reflects tacrolimus-associated immunosuppressive burden and BK viremia risk after kidney transplantation -An observational cohort study

Abstract

Background: Kidney transplantation (KT) is the current treatment of choice in patients with end-stage kidney disease. Immunosuppression is required to prevent acute rejection but is associated with a high incidence of adverse events. The immunosuppressive burden substantially differs between individuals, necessitating new immune monitoring strategies to achieve personalization of immunosuppression. Methods: To compare the evolution of T cell profiles in correlation with immunosuppression and clinical outcomes, 87 kidney transplant recipients were followed for 12 months after KT. Flow cytometry along with assessment of T cell activation markers and clinical data was performed before KT and during study visits 10 days, 2 months and 12 months after KT. Results:Longitudinal T cell phenotyping revealed a significant decrease of T cell activation markers HLA-DR, FCRL3, and CD147 in CD4 + effector T cells after KT. The most pronounced reduction (75%) was found for the activationproliferation marker HLA-DR, which persisted throughout the observational period. The decrease in HLA-DR expression reflected immunosuppressive burden through strong associations with tacrolimus trough-level exposure (coeff=-0.39, p<0.01) and BK viremia incidence (coeff=-0.40, p<0.01) in multivariable regression analysis. Conclusions: T cell activation marker HLA-DR emerges as a potential biomarker for tacrolimus-related immunosuppressive burden in association with BK viremia risk following KT.