Christians Uwe, Klawitter Jelena, Klawitter Jost
iC42 Clinical Research and Development, University of Colorado, Aurora.
Ther Drug Monit. 2016 Apr;38 Suppl 1(Suppl 1):S70-4. doi: 10.1097/FTD.0000000000000243.
Modern multianalyte "omics" technologies allow for the identification of molecular signatures that confer significantly more information than measurement of a single parameter as typically used in current medical diagnostics. Proteomics and metabolomics bioanalytical assays capture a large set of proteins and metabolites in body fluids, cells, or tissues and, complementing genomics, assess the phenome. Proteomics and metabolomics contribute to the development of novel predictive clinical biomarkers in transplantation in 2 ways: they can be used to generate a diagnostic fingerprint or they can be used to discover individual proteins and metabolites of diagnostic potential. Much fewer metabolomics than proteomics biomarker studies in transplant patients have been reported, and, in contrast to proteomics discovery studies, new lead metabolite markers have yet to emerge. Most clinical proteomics studies have been discovery studies. Several of these studies have assessed diagnostic sensitivity and specificity. Nevertheless, none of these newly discovered protein biomarkers have yet been implemented in clinical decision making in transplantation. The currently most advanced markers discovered in proteomics studies in transplant patients are the chemokines CXCL-9 and CXCL-10, which have successfully been validated in larger multicenter trials in kidney transplant patients. These chemokines can be measured using standard immunoassay platforms, which should facilitate clinical implementation. Based on the published evidence, it is reasonable to expect that these chemokine markers can help guiding and individualizing immunosuppressive regimens, may be able to predict acute and chronic T-cell-mediated and antibody-mediated rejection, and may be useful tools for risk stratification of kidney transplant patients.
现代多分析物“组学”技术能够识别分子特征，这些特征所提供的信息比当前医学诊断中通常使用的单一参数测量要多得多。蛋白质组学和代谢组学生物分析检测可捕获体液、细胞或组织中的大量蛋白质和代谢物，并与基因组学相辅相成，评估表型组。蛋白质组学和代谢组学通过两种方式促进移植领域新型预测性临床生物标志物的开发：它们可用于生成诊断指纹，或用于发现具有诊断潜力的单个蛋白质和代谢物。与移植患者的蛋白质组学生物标志物研究相比，代谢组学的相关研究报道要少得多，而且与蛋白质组学发现研究不同的是，尚未出现新的主要代谢物标志物。大多数临床蛋白质组学研究都是发现性研究。其中一些研究评估了诊断敏感性和特异性。然而，这些新发现的蛋白质生物标志物尚未应用于移植临床决策。目前在移植患者蛋白质组学研究中发现的最先进标志物是趋化因子CXCL-9和CXCL-10，它们已在肾移植患者的大型多中心试验中成功得到验证。这些趋化因子可使用标准免疫分析平台进行测量，这应有助于临床应用。基于已发表的证据，有理由期望这些趋化因子标志物能够帮助指导免疫抑制方案并实现个体化，可能能够预测急性和慢性T细胞介导的以及抗体介导的排斥反应，并且可能是肾移植患者风险分层的有用工具。
