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
Department of Internal Medicine 1, University Hospital Rotterdam-Dijkzigt, Rotterdam, The Netherlands.
J Heart Lung Transplant. 1998 Apr;17(4):363-73.
To determine mechanisms that trigger graft vascular disease (GVD) after heart transplantation, we studied parameters that reflect both early and late intragraft allogeneic reactions.
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).
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.
Nonspecific risk factors and IL-2-positive rejections may independently trigger GVD after clinical heart transplantation.
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。
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。
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。
非特异性危险因素和IL-2阳性排斥反应可能在临床心脏移植后独立引发GVD。
