Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand; Department of Internal Medicine, Division of Nephrology and Transplantation, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands; Erasmus MC Transplantation Institute, Rotterdam, the Netherlands.
Research Affairs, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Clin Biochem. 2021 Aug;94:1-11. doi: 10.1016/j.clinbiochem.2021.04.011. Epub 2021 Apr 18.
Acute rejection remains an important problem after kidney transplantation. Enzyme-linked immunosorbent spot (ELISPOT) assay has been investigated extensively and has shown promising results as a predictor of allograft rejection. The objective of this study was to systematically review and analyze the predictive value of the donor-specific ELISPOT assay to identify recipients at risk for acute rejection. Electronic databases were searched for studies reporting donor-specific ELISPOT and kidney transplantation outcomes. Odds ratio (OR) for acute rejection was calculated, along with standardized mean difference (SMD) of cytokine producing-cells between recipients with and without acute rejection. Pooled estimates were calculated using random-effect models. The positive ELISPOT cutoff frequencies were extracted from each study. From 665 articles found, 32 studies were included in the meta-analysis. IFN-γ was the most investigated cytokine (30 out of 32 studies). Patients with positive pre-transplantation donor-reactive IFN-γ ELISPOT had an OR of 3.3 for acute rejection (95%-CI 2.1 to 5.1), and OR of 6.8 (95%-CI 2.5 to 18.9) for post-transplantation ELISPOT. Recipients with rejection had significantly higher frequencies of pre- and post-transplantation cytokine producing-cells (SMD 0.47, 95%-CI 0.07 to 0.87 and SMD 3.68, 95%-CI 1.04 to 6.32, respectively). Pre-transplantation ELISPOT had a positive predictive value of 43% and a negative predictive value of 81% for acute rejection. A positive ELISPOT result was associated with a lower estimated glomerular filtration rate (SMD -0.59, 95%-CI -0.83 to -0.34). In conclusion, patients with a high frequency of donor-reactive IFN-γ ELISPOT are at higher risk for acute rejection. The donor-specific IFN-γ ELISPOT assay can serve as an immune-monitoring tool in kidney transplantation.
急性排斥反应仍是肾移植后的一个重要问题。酶联免疫斑点（ELISPOT）分析已被广泛研究，并已显示出作为移植物排斥预测指标的有前途的结果。本研究的目的是系统地回顾和分析供体特异性 ELISPOT 分析的预测价值，以确定发生急性排斥反应的风险受体。电子数据库中搜索了报告供体特异性 ELISPOT 和肾移植结果的研究。计算了急性排斥反应的优势比（OR），以及有和没有急性排斥反应的受体之间产生细胞因子的标准化均数差（SMD）。使用随机效应模型计算了汇总估计值。从每项研究中提取阳性 ELISPOT 截止频率。从 665 篇文章中，有 32 项研究纳入了荟萃分析。IFN-γ 是研究最多的细胞因子（32 项研究中的 30 项）。移植前具有阳性供体反应性 IFN-γ ELISPOT 的患者发生急性排斥反应的 OR 为 3.3（95%-CI 2.1 至 5.1），移植后 ELISPOT 的 OR 为 6.8（95%-CI 2.5 至 18.9）。发生排斥反应的受者具有明显更高的移植前和移植后产生细胞因子的细胞频率（SMD 0.47，95%-CI 0.07 至 0.87 和 SMD 3.68，95%-CI 1.04 至 6.32）。移植前 ELISPOT 对急性排斥反应的阳性预测值为 43%，阴性预测值为 81%。ELISPOT 阳性结果与估计肾小球滤过率降低有关（SMD -0.59，95%-CI -0.83 至 -0.34）。总之，具有高频率供体反应性 IFN-γ ELISPOT 的患者发生急性排斥反应的风险更高。供体特异性 IFN-γ ELISPOT 分析可作为肾移植中的免疫监测工具。
