Hillman Center for Pediatric Transplantation, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, USA.
Curr Opin Organ Transplant. 2010 Jun;15(3):349-56. doi: 10.1097/MOT.0b013e328339489c.
Immune monitoring is needed in small bowel transplantation (SBTx) because of a high incidence of rejection and graft loss, and life-threatening complications of high-dose prophylactic immunosuppression.
Clinical tests relevant to SBTx include methods to detect antidonor human leukocyte antigen antibodies, among which those which use known purified human leukocyte antigen peptides as substrates correlate best with graft loss; enumerate peripheral lymphocyte subsets to determine the efficacy of lymphocyte-depleting antibodies; estimate general immune function based on ATP production by mitogen-stimulated T-helper cells. Research tests that show clinical utility in SBTx recipients include following markers. First, flow cytometric mixed leukocyte responses, which detect donor-induced proliferation of recipient T-cytotoxic cells by dilution of the intravital dye carboxyfluorescein succinimidyl ester, or donor-induced CD154 expression in recipient T-cytotoxic memory cells. Among such tests, CD154 T-cytotoxic memory cells achieve the highest known sensitivity and specificity of at least 90% for the detection of acute cellular rejection. Second, elevated fecal calprotectin, an early screening marker for intestinal inflammation, which can indicate the need for a SBTx biopsy, especially after ileostomy stoma closure. Third, single-nucleotide polymorphisms associated with inflammatory bowel diseases, for example, nucleotide-binding oligomerization protein, macrophage stimulating 1, and so on. These single-nucleotide polymorphisms may be used to select the rejection-prone SBTx recipient for more potent immunosuppression, if additional studies confirm their associations with outcomes.
The final approach to monitor the SBTx recipient will likely involve using the method(s) with the best sensitivity and specificity for detecting acute cellular rejection or graft loss during time periods when such events are most likely.
小肠移植(SBTx)需要免疫监测,因为排斥反应和移植物丢失的发生率高,且大剂量预防性免疫抑制会产生危及生命的并发症。
与 SBTx 相关的临床检测包括检测抗供体人类白细胞抗原抗体的方法,其中使用已知纯化的人类白细胞抗原肽作为底物的方法与移植物丢失相关性最佳;计数外周淋巴细胞亚群以确定淋巴细胞耗竭抗体的疗效;根据有丝分裂原刺激的辅助 T 细胞产生的三磷酸腺苷来估计总体免疫功能。在 SBTx 受者中显示出临床应用价值的研究检测包括以下标志物。首先,流式细胞术混合白细胞反应,通过稀释活体染料羧基荧光素琥珀酰亚胺酯来检测供体诱导的受体细胞毒性 T 细胞增殖,或供体诱导的受体细胞毒性记忆 T 细胞中 CD154 的表达。在这些检测中,CD154 细胞毒性记忆 T 细胞达到了最高的已知灵敏度和特异性,对于急性细胞排斥的检测灵敏度和特异性至少为 90%。其次,粪便钙卫蛋白升高,这是一种肠道炎症的早期筛查标志物,尤其是在回肠造口关闭后,可以提示需要进行 SBTx 活检。第三,与炎症性肠病相关的单核苷酸多态性,例如核苷酸结合寡聚化结构域蛋白 1、巨噬细胞刺激蛋白 1 等。如果进一步的研究证实这些单核苷酸多态性与结果有关,那么这些单核苷酸多态性可能被用于选择排斥倾向高的 SBTx 受者进行更有效的免疫抑制治疗。
监测 SBTx 受者的最终方法可能涉及使用具有最佳灵敏度和特异性的方法来检测急性细胞排斥或移植物丢失,尤其是在最有可能发生这些事件的时间段内。