McDaniel D O, Zhou X, Moore C K, Aru G
Department of Surgery, University of Mississippi Medical Center, Jackson, Mississippi 39216-4505, USA.
Transplant Proc. 2010 Dec;42(10):4235-7. doi: 10.1016/j.transproceed.2010.09.091.
Evidence suggests that injury-induced activation of the recipient's innate immune response determines the outcome of allograft transplantation. The mechanism responsible for the induction of such innate immune response is not clear yet. We hypothesized that in cardiac transplantation settings, the initial myocardial ischemia and postischemia graft reperfusion may release allograft inflammatory factor (AIF) 1, causing Toll-like receptor (TLR)-mediated activation of macrophages and dendritic cells, leading to the production of cytokines and the activation of adaptive alloimmunity. Therefore, our goal was to validate the presence of these biomarkers in the peripheral blood and biopsy specimens of patients presenting allograft rejection.
We studied 90 peripheral blood and 30 endomyocardial biopsy specimens from patients who had undergone cardiac transplantation. Specimens were tested by quantitative reverse-transcription polymerase chain reaction to determine TLR-2 and -4 and AIF-1 expression levels, correlating with clinical rejection grades. The group differences for mRNA transcript levels between the rejection grades were determined by 1-way analysis of variance. The level of significance was set at P < .05 for comparison between the groups.
The mean ± SEM level of TLR-2 mRNA expression was increased 1.7-fold in monocytes (P < .05) and 4.2-fold in biopsy samples from groups with grade 3A compared with grade 1A or grade 0 rejection (P < .0001). AIF-1 expression was increased 2.4-fold in monocytes (P < .05) and 4.2-fold in biopsy samples comparing grade 3A versus 1A rejections. The TLR-4 mRNA expression was also increased in the group with 3A rejections; however, the difference was only significant in biopsy specimens (P < .0001).
Our data demonstrated that expression profiles of AIF-1 and TLR-2 correlated with biopsy-proven allograft rejection in both peripheral blood and local tissue, suggesting their potential as diagnostic biomarkers for early detection of allograft rejection.
有证据表明，损伤诱导的受体固有免疫反应激活决定了同种异体移植的结果。然而，引发这种固有免疫反应的机制尚不清楚。我们推测，在心脏移植过程中，最初的心肌缺血和缺血后移植物再灌注可能会释放同种异体移植炎症因子（AIF）1，导致Toll样受体（TLR）介导的巨噬细胞和树突状细胞激活，进而导致细胞因子产生和适应性同种免疫激活。因此，我们的目标是验证这些生物标志物在发生同种异体移植排斥反应患者的外周血和活检标本中的存在情况。
我们研究了90份心脏移植患者的外周血标本和30份心内膜活检标本。通过定量逆转录聚合酶链反应检测标本，以确定TLR-2和-4以及AIF-1的表达水平，并与临床排斥反应分级相关联。通过单因素方差分析确定不同排斥反应分级之间mRNA转录水平的组间差异。设定显著性水平为P <.05用于组间比较。
与1A或0级排斥反应组相比，3A级组单核细胞中TLR-2 mRNA表达的平均±标准误水平增加了1.7倍（P <.05），活检样本中增加了4.2倍（P <.0001）。比较3A级与1A级排斥反应时，单核细胞中AIF-1表达增加了2.4倍（P <.05），活检样本中增加了4.2倍。3A级排斥反应组中TLR-4 mRNA表达也增加；然而，差异仅在活检标本中显著（P <.0001）。
我们的数据表明，AIF-1和TLR-2的表达谱与外周血和局部组织中经活检证实的同种异体移植排斥反应相关，表明它们作为早期检测同种异体移植排斥反应的诊断生物标志物的潜力。
