Department of Surgery, Far Eastern Memorial Hospital, New Taipei City, Taiwan.
Graduate Institute of Medicine, Yuan Ze University, Taoyuan, Taiwan.
Transpl Int. 2023 Sep 8;36:11595. doi: 10.3389/ti.2023.11595. eCollection 2023.
Diagnosing acute rejection after intestinal transplantation currently heavily relies on histopathological analysis of graft biopsies. However, the invasive risks associated with ileoscopic examination and the inaccessibility for biopsy after ileostomy closure hinder real-time detection of rejection responses. Molecules comprising the intestinal barrier have been identified as physiological and molecular biomarkers for various bowel conditions and systemic diseases. To investigate the potential of barrier function-related molecules in diagnosing rejection after intestinal transplantation, plasma samples were collected longitudinally from transplant recipients. The samples were categorized into "indeterminate for rejection (IND)" and "acute rejection (AR)" groups based on clinical diagnoses at each time point. The longitudinal association between plasma levels of these barrier function-related molecules and acute rejection was analyzed using the generalized estimating equations (GEE) method. Logistic GEE models revealed that plasma levels of claudin-3, occludin, sIgA, and zonulin were independent variables correlated with the clinical diagnosis of acute rejection. The subsequent prediction model demonstrated moderate ability in discriminating between IND and AR samples, with a sensitivity of 76.0%, specificity of 89.2%, and accuracy of 84.6%. In conclusion, monitoring plasma levels of claudin-3, occludin, sIgA, and zonulin shows great potential in aiding the diagnosis of acute rejection after intestinal transplantation.
目前,诊断肠移植后的急性排斥反应主要依赖于移植活检的组织病理学分析。然而,经内镜检查存在侵入性风险,回肠造口关闭后无法进行活检,这阻碍了排斥反应的实时检测。肠道屏障相关的分子已被确定为各种肠道疾病和系统性疾病的生理和分子生物标志物。为了研究肠屏障功能相关分子在诊断肠移植后排斥反应中的潜力,从移植受者中纵向采集了血浆样本。根据每个时间点的临床诊断,将样本分为“不确定排斥(IND)”和“急性排斥(AR)”组。使用广义估计方程(GEE)方法分析这些屏障功能相关分子的血浆水平与急性排斥之间的纵向关联。逻辑 GEE 模型显示,Claudin-3、occludin、sIgA 和 zonulin 的血浆水平是与急性排斥临床诊断相关的独立变量。随后的预测模型表明,区分 IND 和 AR 样本的能力中等,其灵敏度为 76.0%,特异性为 89.2%,准确性为 84.6%。总之,监测 Claudin-3、occludin、sIgA 和 zonulin 的血浆水平在辅助诊断肠移植后的急性排斥反应方面具有很大的潜力。