Israeli Moshe, Yussim Alex, Mor Eitan, Sredni Benjamin, Klein Tirza
Tissue Typing Laboratory, Rabin Medical Center, Petach, Tikva, Israel.
Transpl Immunol. 2007 Jul;18(1):7-12. doi: 10.1016/j.trim.2007.03.005. Epub 2007 Apr 9.
The survival of a transplanted organ is dependent on maintenance of continuous immunosuppression. However, even the strictest adherence to the recommended drug levels does not prevent the occurrence of numerous complications associated with immunosuppression. The efficacy of immunosuppression therapy protocols would be enhanced greatly by the availability of biotechnologies capable of identifying and predicting immunological events prior to the manifestation of clinical parameters indicating graft failure. The aim of the study was to evaluate the potential contribution of some modern tools for post-transplantation monitoring, and to propose a method for combining them into a comprehensive mechanism for this purpose. The technologies utilized in this study are among a group of 'cutting edge' diagnostic methods at the initial steps of evaluation for their potential contribution for post-transplantation immune monitoring. This study was a pioneering opportunity to combine and utilize these tools jointly. The method of research was based on monitoring 13 adult kidney transplant recipients. The Immuknow assay determined cellular immunity status by quantitative measurement of intracellular ATP level in CD4(+) lymphocytes after PHA stimulation. Sera were analyzed for concentration of soluble CD30 reflecting primary allo-stimulation and for donor specific anti-HLA antibodies responsible for accelerated and refractory rejection. The results were correlated with clinical and pathological parameters and appraisal of predictive value was attempted. In Immuknow assay analysis ATP incremental changes indicative of rejection or infection were found in 75% and in 50% incidences, respectively. In stable patients, the ATP deviation from the preoperative baseline, indicative of stable engraftment, was much less pronounced than in other habitual clinical tests. CD30 concentrations were measured greatly above normal values prior to biopsy-proven rejection episodes, both before and after the transplant operation. Anti-HLA antibodies were elevated at a later stage, concurrently with clinical manifestation of graft failure and rejection. Anti-HLA antibody level remained negligible in patients going through a stable post-transplant clinical course. Overall, the utilization of the platform of combined biotechnologies could serve as a valuable tool for immune monitoring in organ transplantation, allowing for therapeutic intervention that can favorably affect the clinical outcome.
移植器官的存活依赖于持续免疫抑制的维持。然而,即使最严格地遵守推荐的药物水平,也无法预防与免疫抑制相关的众多并发症的发生。如果有能够在表明移植失败的临床参数出现之前识别和预测免疫事件的生物技术,免疫抑制治疗方案的疗效将大大提高。本研究的目的是评估一些现代工具对移植后监测的潜在贡献,并提出一种将它们组合成一个综合机制的方法。本研究中使用的技术是一组“前沿”诊断方法中的一部分,正处于评估其对移植后免疫监测潜在贡献的初始阶段。本研究是联合使用这些工具的开创性机会。研究方法基于对13名成年肾移植受者的监测。免疫状态检测通过定量测量PHA刺激后CD4(+)淋巴细胞内的ATP水平来确定细胞免疫状态。分析血清中反映初次同种异体刺激的可溶性CD30浓度以及负责加速和难治性排斥反应的供体特异性抗HLA抗体。将结果与临床和病理参数相关联,并尝试评估预测价值。在免疫状态检测分析中,分别在75%和50%的病例中发现了指示排斥或感染的ATP增量变化。在病情稳定的患者中,与术前基线相比ATP的偏差表明移植稳定,其程度远不如其他常规临床检测明显。在经活检证实的排斥发作之前,无论是移植手术前还是手术后,CD30浓度的测量值都大大高于正常值。抗HLA抗体在后期升高,同时伴有移植失败和排斥反应的临床表现。在移植后临床过程稳定的患者中,抗HLA抗体水平仍然可以忽略不计。总体而言,联合生物技术平台的应用可作为器官移植免疫监测的有价值工具,允许进行能对临床结果产生有利影响的治疗干预。