MOLECULAR CHARACTERIZATION OF LIVER ALLOGRAFTS FROM OPERATIONALLY TOLERANT TRANSPLANT RECIPIENTS (Affymetrix). Homo sapiens

In clinical organ transplantation complete cessation of immunosuppressive therapy can be successfully accomplished in selected recipients providing a proof-of-principle that allograft tolerance is attainable in humans. The intra-graft molecular pathways associated with human allograft tolerance, however, have not been comprehensively studied before. In this study we analyzed sequential liver tissue samples collected from liver recipients enrolled in a prospective multicenter immunosuppressive withdrawal clinical trial. Tolerant and non-tolerant recipients differed in the intra-graft expression of genes involved in the regulation of iron homeostasis.These results point to a critical role of iron homeostasis in the regulation of intra-graft alloimmune responses in humans and provide a set of novel biomarkers to conduct drug-weaning trials in liver transplantation. Overall design: The complete database comprised the expression measurements of 54,675 genes for liver inmunotolerance groups: 9 Tolerant (TOL) 10 Non Tolerant (Non TOL).A subset of 5 tolerant samples (TOL POST) were taken 1 year after inmunosuppresive therapy.

在临床器官移植领域中，对筛选后的受者成功完全停用免疫抑制治疗，可为人类同种移植物耐受（allograft tolerance）的可行性提供原理性验证。然而，目前尚未对与人类同种移植物耐受相关的移植物内分子通路开展全面研究。
本研究针对一项前瞻性多中心免疫抑制撤除临床试验中纳入的肝移植受者的系列肝组织样本进行了分析。耐受组与非耐受组受者的移植物内铁稳态（iron homeostasis）调控相关基因的表达存在显著差异。
本研究结果提示，铁稳态在人类移植物内同种异体免疫应答调控中发挥关键作用，并为肝移植领域的药物撤除试验提供了一系列新型生物标志物。
整体设计：完整数据库包含了肝免疫耐受（immunotolerance）组共54675个基因的表达量检测数据，其中耐受组（TOL）9例、非耐受组（Non TOL）10例；另有5例耐受组样本（TOL POST）采集于免疫抑制治疗撤除1年后。