Enzyme-linked immunosorbent spot assay for donor-reactive interferon-gamma-producing cells identifies T-cell presensitization and correlates with graft function at 6 and 12 months in renal-transplant recipients
Enzyme-linked immunosorbent spot assay for donor-reactive interferon-gamma-producing cells identifies T-cell presensitization and correlates with graft function at 6 and 12 months in renal-transplant recipients
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DOI：
10.1097/01.tp.0000144057.31799.6a
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发表时间：
2004-12-15
期刊：
影响因子：
6.2
通讯作者：
Reinke, P
中科院分区：
文献类型：
--
作者：
Nickel, P;Presber, F;Reinke, P
背景。临床移植的一个主要目标是免疫抑制的个体化。这就需要一个标志物的定义，以识别急性排斥反应和免疫介导的慢性同种异体移植肾病的高风险患者。在未选择的肾移植患者中，采用酶联免疫吸附斑点法（ELISPOT）连续测定了移植前（n=42）和移植后前6个月（n=48）多达10次（平均5.0）的干扰素- γ产生供体反应细胞的频率，以确定详细的动力学并分析其与移植后6个月和12个月急性排斥反应和移植物功能的相关性。移植前ELISPOT频率在急性排斥患者（16/42）中显著高于非排斥患者（26/42）。移植前高频率（外周血单个核细胞[PBMCs]， n=5/42）与严重急性排斥发作的风险相关，但与高面板反应性抗体等危险因素无关。早期移植物衰竭仅发生在该组。重要的是，移植后第2周和第3周而不是第6个月的平均ELISPOT频率与6个月和12个月的肾小球滤过率呈负相关。在无急性排斥反应的患者中，ELISPOT频率与肾功能的相关性最高。移植前ELISPOT检测可能有助于识别t细胞现敏患者，这些患者发生严重早期急性排斥反应的风险较高。在移植后早期对ELISPOT供体反应性细胞进行分析，可能有助于识别有免疫介导的移植物恶化风险的患者。
Background. A major goal in clinical transplantation is the individualization of immunosuppression. This requires a definition of markers that identify patients at heightened risk of acute rejection and immune-mediated chronic allograft nephropathy.Methods. Frequencies of interferon-gamma-producing donor-reactive cells were serially determined in unselected renal-transplant patients in an enzyme-linked immunosorbent spot assay (ELISPOT) before transplantation (n=42) and up to 10 (mean 5.0) times during the first 6 months posttransplantation (n=48) to determine detailed kinetics and analyze for correlation with acute rejection and graft function at 6 and 12 months posttransplantation.Results. Pretransplant ELISPOT frequencies were significantly higher in patients with acute rejection (16/42) versus nonrejecters (26/42). Highly elevated pretransplant frequencies (>200 spots/300,000 peripheral blood mononuclear cells [PBMCs], n=5/42) were associated with a risk of severe acute rejection episodes but were independent of risk factors such as high panel reactive antibodies. Early graft failure exclusively occurred in this group. Importantly, mean ELISPOT frequencies at weeks 2 and 3 but not at month 6 posttransplant correlated inversely with 6 and 12 months glomerular filtration rate. The correlation between ELISPOT frequencies and renal function showed the highest significance in patients without acute rejection.Conclusions. The pretransplant ELISPOT assay might be useful to identify T-cell presensitized patients, who are at heightened risk for severe early acute rejection. An analysis of ELISPOT donor-reactive cells during the early posttransplant period might allow an identification of patients at risk for immune-mediated graft deterioration.