急性排斥反应的本质与临床心脏移植后移植血管疾病的发生有关。

The nature of acute rejection is associated with development of graft vascular disease after clinical heart transplantation.

作者信息

Baan C C, Holweg C T, Niesters H G, van Gelder T, Mol W M, Zondervan P E, Mochtar B, Balk A H, Weimar W

机构信息

Department of Internal Medicine 1, University Hospital Rotterdam-Dijkzigt, Rotterdam, The Netherlands.

出版信息

J Heart Lung Transplant. 1998 Apr;17(4):363-73.

PMID:9588581

Abstract

BACKGROUND

To determine mechanisms that trigger graft vascular disease (GVD) after heart transplantation, we studied parameters that reflect both early and late intragraft allogeneic reactions.

METHOD

With reverse transcriptase-polymerase chain reaction analysis, mRNA expression of interleukin-2 (IL-2), interleukin-4, interleukin-6, interleukin-10, interferon-gamma, platelet-derived growth factor-alpha, and transforming growth factor-beta was measured in endomyocardial biopsy (EMB) specimens obtained from 34 recipients during the first acute rejection episode (n = 29) or at a comparable time after transplantation for patients without rejection (n = 5) and at time of assessment of GVD by coronary angiography at 1 year (n = 34).

RESULTS

At the time of assessment of GVD, mRNA expression of IL-2, interleukin-4, and interleukin-6 were barely detectable, whereas messenger coding for interferon-gamma, interleukin-10, transforming growth factor-beta, and platelet-derived growth factor-alpha genes were constitutively expressed. Moreover, intragraft mRNA patterns of cytokines and growth factors between patients with GVD (n = 17) or without GVD (n = 17) were comparable. In contrast, during the first acute rejection episode a completely different pattern was found. Development of GVD was associated with IL-2 mRNA expression and not with the other cytokines analyzed. IL-2 mRNA was present in 77% of rejection EMB specimens obtained from patients with GVD versus 33% of the EMB specimens obtained from patients without GVD (p = 0.03) and not detectable in EMB specimens obtained from patients with no rejection. Also nonimmunologic risk factors such as longer ischemia time (median 193 vs 141 minutes; p = 0.002) and higher donor age (median 32 vs 23 years; p = 0.02) were associated with GVD. But no relation was found between these nonimmunologic risk factors and IL-2-positive acute rejections.

CONCLUSIONS

Nonspecific risk factors and IL-2-positive rejections may independently trigger GVD after clinical heart transplantation.

摘要

背景

为了确定心脏移植后引发移植血管病（GVD）的机制，我们研究了反映早期和晚期移植内同种异体反应的参数。

方法

采用逆转录-聚合酶链反应分析，在34例受者的心内膜心肌活检（EMB）标本中检测白细胞介素-2（IL-2）、白细胞介素-4、白细胞介素-6、白细胞介素-10、干扰素-γ、血小板衍生生长因子-α和转化生长因子-β的mRNA表达。这些标本取自34例受者，其中29例处于首次急性排斥反应期，5例无排斥反应的受者在移植后相当时间取材，34例在1年时通过冠状动脉造影评估GVD时取材。

结果

在评估GVD时，IL-2、白细胞介素-4和白细胞介素-6的mRNA表达几乎检测不到，而编码干扰素-γ、白细胞介素-10、转化生长因子-β和血小板衍生生长因子-α基因的信使RNA呈组成性表达。此外，有GVD（n = 17）和无GVD（n = 17）患者的移植内细胞因子和生长因子mRNA模式相当。相比之下，在首次急性排斥反应期发现了完全不同的模式。GVD的发生与IL-2 mRNA表达有关，与所分析的其他细胞因子无关。有GVD患者的排斥EMB标本中77%存在IL-2 mRNA，无GVD患者的EMB标本中这一比例为33%（p = 0.03），无排斥反应患者的EMB标本中未检测到IL-2 mRNA。较长的缺血时间（中位数193分钟对141分钟；p = 0.002）和较高的供体年龄（中位数32岁对23岁；p = 0.02）等非免疫危险因素也与GVD有关。但这些非免疫危险因素与IL-2阳性急性排斥反应之间未发现关联。