Schoels M, Dengler T J, Richter R, Meuer S C, Giese T
Institute of Immunology, University of Heidelberg, Heildelberg, Germany.
Clin Transplant. 2004 Oct;18(5):513-7. doi: 10.1111/j.1399-0012.2004.00197.x.
Detection of cardiac allograft rejection is based on the histological examination of endomyocardial biopsies (EMB). We have explored the possibility of whether graft rejection could be detected by characteristic gene expression patterns in peripheral blood mononuclear cells (PBMC) of heart-transplant recipients.
The study included 58 blood samples of 44 patients. On the day of EMB, mononuclear cells were isolated from peripheral blood, and gene expression was measured by quantitative real-time PCR. Thirty-nine parameters, including cytokine and chemokine genes were analyzed. Gene expression results were correlated with histological assessment of concomitant evaluated EMB according to International Society for Heart and Lung Transplantation (ISHLT) nomenclature.
Gene expression of perforin, CD95 ligand, granzyme B, RANTES, CXCR3, COX2, ENA 78 and TGF-beta1 was significantly different in PBMC of patients with mild to moderate degrees of allograft rejection (> or =grade 2) compared with patients exhibiting no or minor forms of rejection (<grade 2). Using discriminance analysis, five parameters were found that allow discrimination of rejection > or =grade 2 vs. <grade 2 with a sensitivity of 84% and a specificity of 82% as assessed by receiver operating characteristic analysis.
Quantitative analysis of gene expression in PBMC may be a valuable tool for non-invasive diagnosis of allograft rejection and may allow further insight in the biological process of graft rejection.
心脏移植排斥反应的检测基于心内膜心肌活检（EMB）的组织学检查。我们探讨了能否通过心脏移植受者外周血单个核细胞（PBMC）中特征性基因表达模式来检测移植排斥反应。
该研究纳入了44例患者的58份血样。在进行EMB当天，从外周血中分离单个核细胞，通过定量实时PCR测定基因表达。分析了包括细胞因子和趋化因子基因在内的39个参数。根据国际心肺移植协会（ISHLT）的命名法，将基因表达结果与同期评估的EMB组织学评估结果进行关联。
与无排斥反应或轻度排斥反应（<2级）的患者相比，轻度至中度移植排斥反应（≥2级）患者的PBMC中穿孔素、CD95配体、颗粒酶B、RANTES、CXCR3、COX2、ENA 78和转化生长因子-β1的基因表达有显著差异。通过判别分析，发现有5个参数可用于区分≥2级排斥反应与<2级排斥反应，经受试者工作特征分析评估，其灵敏度为84%，特异性为82%。
PBMC中基因表达的定量分析可能是一种用于移植排斥反应无创诊断的有价值工具，并且可能有助于进一步深入了解移植排斥反应的生物学过程。
