Mehra Mandeep R, Kobashigawa Jon A, Deng Mario C, Fang Kenneth C, Klingler Tod M, Lal Preeti G, Rosenberg Steven, Uber Patricia A, Starling Randall C, Murali Srinivas, Pauly Daniel F, Dedrick Russell, Walker Michael G, Zeevi Adriana, Eisen Howard J
Division of Cardiology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
J Heart Lung Transplant. 2007 Dec;26(12):1255-63. doi: 10.1016/j.healun.2007.09.009. Epub 2007 Nov 26.
Profiling mRNA levels of 11 informative genes expressed by circulating immune effector cells identifies cardiac allograft recipients at low risk for current moderate-severe acute cellular rejection (ACR).
We conducted a nested case-control study of 104 cardiac allograft recipients to investigate the association of transcriptional profiles of blood samples with either a future rejection episode within 12 weeks of a baseline clinical sample or persistent histologic quiescence for the same time period.
The transcription profile yielded a score (0 to 40 scale) of 27.4 +/- 6.3 for future rejectors (n = 39) and 23.9 +/- 7.1 for controls (n = 65) (p = 0.01). In patients who were <or=180 days post-transplant, the gene expression score was 28.4 +/- 4.9 for rejectors (n = 28) and 22.4 +/- 7.5 for controls (n = 48) (p < 0.001). In this period, no samples from patients who went on to reject within 12 weeks had gene expression scores of <20. Differential expression of the gene IL1R2 was significantly associated with future events. Of 33 additional genes profiled, 5 supported corticosteroid-sensitive constituents (IL1R2 and FLT3), whereas 6 supported T-cell activation (PDCD1).
These data suggest that pathways regulating T-cell homeostasis and corticosteroid sensitivity are associated with future ACR in cardiac allografts and suggest that these signals are evident before histologically detectable rejection.
分析循环免疫效应细胞表达的11个信息基因的mRNA水平，可识别出当前发生中度至重度急性细胞排斥反应（ACR）风险较低的心脏移植受者。
我们对104名心脏移植受者进行了一项巢式病例对照研究，以调查血液样本转录谱与基线临床样本后12周内未来排斥反应发作或同一时期持续组织学静止之间的关联。
未来发生排斥反应者（n = 39）的转录谱得分为27.4±6.3（0至40分），对照组（n = 65）为23.9±7.1（p = 0.01）。在移植后≤180天的患者中，发生排斥反应者（n = 28）的基因表达得分为28.4±4.9，对照组（n = 48）为22.4±7.5（p < 0.001）。在此期间，在12周内发生排斥反应的患者中，没有样本的基因表达得分<20。基因IL1R2的差异表达与未来事件显著相关。在另外分析的33个基因中，5个支持对皮质类固醇敏感的成分（IL1R2和FLT3），而6个支持T细胞活化（PDCD1）。
这些数据表明，调节T细胞稳态和皮质类固醇敏感性的途径与心脏移植未来的ACR相关，并且表明这些信号在组织学可检测到的排斥反应之前就很明显。
