Khatri Purvesh, Sarwal Minnie M
Division of Nephrology, Department of Pediatrics, Stanford University, Stanford, California, USA.
Curr Opin Organ Transplant. 2009 Feb;14(1):34-9. doi: 10.1097/MOT.0b013e32831e13d0.
In the last decade, microarray technology has revolutionized biological research by allowing the screening of tens of thousands of genes simultaneously. This article reviews recent studies in organ transplantation using microarrays and highlights the issues that should be addressed in order to use microarrays in diagnosis of rejection.
Microarrays have been useful in identifying potential biomarkers for chronic rejection in peripheral blood mononuclear cells, novel pathways for induction of tolerance, and genes involved in protecting the graft from the host immune system. Microarray analysis of peripheral blood mononuclear cells from chronic antibody-mediated rejection has identified potential noninvasive biomarkers. In a recent study, correlation of pathogenesis-based transcripts with histopathologic lesions is a promising step towards inclusion of microarrays in clinics for organ transplants.
Despite promising results in diagnosis of histopathologic lesions using microarrays, the low dynamic range of microarrays and large measured expression changes within the probes for the same gene continue to cast doubts on their readiness for diagnosis of rejection. More studies must be performed to resolve these issues. Dominating expression of globin genes in whole blood poses another challenge for identification of noninvasive biomarkers. In addition, studies are also needed to demonstrate effects of different immunosuppression therapies and their outcomes.
在过去十年中,微阵列技术通过允许同时筛选数万个基因,给生物学研究带来了变革。本文综述了近期使用微阵列技术进行器官移植研究的情况,并强调了在将微阵列技术用于排斥反应诊断时需要解决的问题。
微阵列技术在识别外周血单核细胞中慢性排斥反应的潜在生物标志物、诱导免疫耐受的新途径以及参与保护移植物免受宿主免疫系统攻击的基因方面发挥了作用。对慢性抗体介导的排斥反应中外周血单核细胞进行微阵列分析,已识别出潜在的非侵入性生物标志物。在最近一项研究中,基于发病机制的转录本与组织病理学病变之间的相关性是朝着将微阵列技术纳入器官移植临床诊断迈出的充满希望的一步。
尽管在使用微阵列技术诊断组织病理学病变方面取得了令人鼓舞的结果,但微阵列技术的低动态范围以及同一基因探针内测量到的较大表达变化,仍让人对其用于排斥反应诊断的准备情况存疑。必须开展更多研究来解决这些问题。全血中珠蛋白基因的主导表达给识别非侵入性生物标志物带来了另一个挑战。此外,还需要开展研究来证明不同免疫抑制疗法的效果及其结果。