Simon Aberger, Max Schuller, Agnes A Mooslechner, Konstantin A Klötzer, Barbara Prietl, Verena Pfeifer, Alexander H Kirsch, Alexander R Rosenkranz, Katharina Artinger, Kathrin Eller
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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. Longitudinal T cell phenotyping revealed a significant decrease of T cell activation markers HLA-DR, FCRL3, and CD147 in CD4<sup>+</sup> effector T cells after KT. The most pronounced reduction (75%) was found for the activation-proliferation 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. 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引用次数: 0
摘要
肾移植(KT)是目前终末期肾病患者的首选治疗方法。免疫抑制是预防急性排斥反应所必需的,但与高发生率的不良事件相关。个体之间的免疫抑制负担有很大差异,需要新的免疫监测策略来实现免疫抑制的个体化。为了比较T细胞谱的演变与免疫抑制和临床结果的相关性,87名肾移植受者在KT后随访了12个月。在KT前和KT后10天、2个月和12个月的研究访问期间进行流式细胞术、T细胞活化标志物和临床数据评估。纵向T细胞表型分析显示,KT后CD4+效应T细胞中T细胞活化标志物HLA-DR、FCRL3和CD147显著降低。激活增殖标志物HLA-DR减少最明显(75%),在整个观察期间持续存在。在多变量回归分析中,HLA-DR表达的下降与他克莫司谷水平暴露(coeff = -0.39, p < 0.01)和BK病毒血症发生率(coeff = -0.40, p < 0.01)密切相关,反映了免疫抑制负担。T细胞活化标志物HLA-DR作为他克莫司相关免疫抑制负担与KT后BK病毒血症风险相关的潜在生物标志物出现。
T cell Activation Marker HLA-DR Reflects Tacrolimus-Associated Immunosuppressive Burden and BK Viremia Risk After Kidney Transplantation - An Observational Cohort Study.
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. 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. 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 activation-proliferation 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. T cell activation marker HLA-DR emerges as a potential biomarker for tacrolimus-related immunosuppressive burden in association with BK viremia risk following KT.
期刊介绍:
The aim of the journal is to serve as a forum for the exchange of scientific information in the form of original and high quality papers in the field of transplantation. Clinical and experimental studies, as well as editorials, letters to the editors, and, occasionally, reviews on the biology, physiology, and immunology of transplantation of tissues and organs, are published. Publishing time for the latter is approximately six months, provided major revisions are not needed. The journal is published in yearly volumes, each volume containing twelve issues. Papers submitted to the journal are subject to peer review.