Goertsches Robert H, Hecker Michael, Zettl Uwe K
Department of Neurology, University of Rostock, Gehlsheimer Strasse 20, 18147 Rostock, Germany.
J Neurol. 2008 Dec;255 Suppl 6:48-57. doi: 10.1007/s00415-008-6010-1.
Applying microarray technology to identify new diagnostic and prognostic markers in peripheral blood cells (PBC) after therapeutic intervention opens great perspectives regarding patient subclassification. Three recombinant products of the pleiotropic agent interferon beta (rIFN-beta) are available for disease modifying therapy of relapsing remitting multiple sclerosis (RRMS), a complex inflammatory autoimmune disease that targets the central nervous system. They differ according to formulation, route of administration and dosage regimens. The currently, only partially understood mechanism of action of injected rIFN-beta into human organisms needs provision with accessory key molecules; in addition, the significance of established clinical IFN-beta response criteria that distinguish responding from non-responding patients remain unclear.With respect to these major questions, we discuss promising candidates on the gene transcription level, attained from scientific MS literature that included a longitudinal aspect. Reviewed studies were in part carried out with distinct gene interrogating platforms (GeneArrays; RT-PCR), settings (in vitro; ex vivo), and study designs (drug formulations and regimen; inclusion criteria and clinical endpoints), hampering meaningful meta-analysis. Nevertheless, PBC from therapy-naïve MS patients, rIFN-beta treated MS patients, and healthy controls served to characterize facets of both the disease and its treatment. Hence, the field of MS transcriptomics in immunomodulatory therapy is (by far) not adequately understood and should be embedded into systems biology disciplines, yielding multi-layer analyses that deliver timely identification of MS subjects who will profit from applied rIFN-beta therapy.
应用微阵列技术识别治疗干预后外周血细胞（PBC）中的新诊断和预后标志物，为患者亚分类提供了广阔前景。三种多效性药物干扰素β（rIFN-β）的重组产品可用于复发缓解型多发性硬化症（RRMS）的疾病改善治疗，RRMS是一种针对中枢神经系统的复杂炎症性自身免疫疾病。它们在制剂、给药途径和剂量方案方面存在差异。目前，注射到人体中的rIFN-β的作用机制仅部分为人所知，需要补充关键分子；此外，区分有反应和无反应患者的既定临床IFN-β反应标准的意义仍不明确。针对这些主要问题，我们在基因转录水平上讨论了从包含纵向研究的多发性硬化症科学文献中获得的有前景的候选物。所综述的研究部分采用了不同的基因检测平台（基因芯片；逆转录聚合酶链反应）、设置（体外；离体）和研究设计（药物制剂和方案；纳入标准和临床终点），这妨碍了有意义的荟萃分析。尽管如此，未经治疗的多发性硬化症患者、接受rIFN-β治疗的多发性硬化症患者和健康对照的外周血细胞用于表征疾病及其治疗的多个方面。因此，免疫调节治疗中多发性硬化症转录组学领域（到目前为止）尚未得到充分理解，应纳入系统生物学学科，进行多层分析，以便及时识别将从应用rIFN-β治疗中获益的多发性硬化症患者。
