Cagnola H, Scaravonati R, Cabanne A, Bianchi C, Gruz F, Errea A, Zambernardi A, Meier D, Chirdo F, Docena G, Gondolesi G, Rumbo M
Universidad Nacional de La Plata, La Plata, Argentina.
Transplant Proc. 2010 Jan-Feb;42(1):57-61. doi: 10.1016/j.transproceed.2009.12.013.
The diagnosis of rejection after intestinal transplantation is still performed by endoscopic biopsy monitoring. Less invasive diagnostic procedures are desirable, although they are not available so far. Calprotectin, a stable cytosolic granulocyte protein, which previously was used as a marker of inflammatory processes, has been proposed to be a biochemical marker for rejection. The aim of the present work was to analyze the concordance between calprotectin levels in intestinal content and the presence of graft rejection after small bowel transplantation.
Calprotectin level was measured using a commercial ELISA kit on 137 samples of intestinal content randomly collected during endoscopies performed on 11 intestinal transplantation patients during 2 years' follow-up. Calprotectin determinations were correlated with histological and clinical findings. The cut-off level was determined retrospectively by receiver-operator curve analysis.
Based on histological findings and clinical records, samples were discerned as rejection positive (37 of 137), versus negative (35 of 137) samples or those with no clinical, endoscopic, or histological findings (65 of 137 samples). A cut-off value of 65 microg of calprotectin/g of intestinal content provided the best assay parameter according to the clinical findings: a 76% sensitivity and a 47% specificity. False positive results corresponded to patients with gastrointestinal infections (13%), systemic infections (13%), ulcers (10%), or nonspecific histological alterations of the mucosa (15%). The other false positive cases corresponded to postsurgical samples (4%), or patients with concomitant gastrointestinal symptoms (2%). Most false negative results (78%) were observed during recovery from severe acute rejection episodes, among successfully treated patients. In these cases, epithelial reconstitution and no mucosal infiltration was observed. If the latter group were discarded, sensitivity rose to 93%, and specificity, to 50% with a 96% negative predictive value. Furthermore, a weak correlation was observed between calprotectin levels and the severity of rejection.
This study confirmed the results obtained by other groups: fecal calprotectin dosage showed a good sensitivity but low specificity for the diagnosis of intestinal rejection because high calprotectin levels can also be observed in other clinical conditions. Nevertheless, it might be used as a first line for continuous evaluation of intestinal transplantation status, like other biochemical parameters that are used in kidney or liver transplantation, before considering the need for a biopsy.
肠道移植后排斥反应的诊断仍通过内镜活检监测进行。尽管目前尚无侵入性较小的诊断方法，但人们期望有此类方法。钙卫蛋白是一种稳定的胞质粒细胞蛋白，以前用作炎症过程的标志物，现已被提议作为排斥反应的生化标志物。本研究的目的是分析小肠移植后肠道内容物中钙卫蛋白水平与移植排斥反应之间的一致性。
使用商用酶联免疫吸附测定（ELISA）试剂盒对11例肠道移植患者在2年随访期间内镜检查时随机采集的137份肠道内容物样本进行钙卫蛋白水平测定。钙卫蛋白测定结果与组织学和临床结果相关。通过受试者操作特征曲线分析回顾性确定临界值。
根据组织学结果和临床记录，样本被区分为排斥反应阳性（137份中的37份）、阴性（137份中的35份）或无临床、内镜或组织学异常（137份样本中的65份）。根据临床结果，肠道内容物中钙卫蛋白含量为65微克/克时为最佳检测参数：敏感性为76%，特异性为47%。假阳性结果对应的患者有胃肠道感染（13%）、全身感染（13%）、溃疡（10%）或黏膜非特异性组织学改变（15%）。其他假阳性病例对应的是术后样本（4%）或伴有胃肠道症状的患者（2%）。大多数假阴性结果（78%）出现在成功治疗的患者从严重急性排斥反应发作中恢复期间。在这些病例中，观察到上皮重建且无黏膜浸润。如果排除后一组，敏感性升至93%，特异性升至50%，阴性预测值为96%。此外，钙卫蛋白水平与排斥反应的严重程度之间存在弱相关性。
本研究证实了其他研究小组的结果：粪便钙卫蛋白检测对肠道排斥反应的诊断具有良好的敏感性，但特异性较低，因为在其他临床情况下也可观察到高钙卫蛋白水平。然而，在考虑是否需要活检之前，它可能像肾移植或肝移植中使用的其他生化参数一样，用作连续评估肠道移植状态的一线方法。
