Detection of donor-specific antibodies using HLA-coated microspheres: another tool for kidney transplant risk stratification

Detection of donor-specific antibodies using HLA-coated microspheres: another tool for kidney transplant risk stratification
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DOI:
10.1093/ndt/gfl202
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发表时间:
2006-09-01
影响因子:
6.1
通讯作者:
Wiseman, Alexander C.
Wiseman, Alexander C.
中科院分区:
医学1区
文献类型:
--
作者:
Gibney, Eric M.;Cagle, Linda R.;Wiseman, Alexander C.

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背景。灵敏的技术能够检测低水平的循环抗体。对于许多新技术来说,这些抗体的临床后果尚不清楚。我们希望确定通过使用基于 Luminex (R) 微球的检测方法检测到的抗体的重要性。 2003 年 3 月至 2004 年 5 月期间接受肾移植且抗人球蛋白增强补体依赖性细胞毒性 (AHG-CDC) 交叉配型呈阴性的患者使用 Luminex 微球和储存血清重新检测移植前反应性抗体 (PRA)。如果 I 类或 II 类 Luminex PRA >= 15%,则认为患者具有循环抗体。然后对这些患者进行移植前供体特异性抗体(DSA)分析。比较接受和不接受 DSA 的患者的临床结果。结果。在 136 名接受移植的患者中,55 名患者的 Luminex PRA >= 15%。在这 55 名患者中,只有 16 名患者的标准 PRA ≥ 30%,75% 的患者有致敏事件史。 55 名患者中有 20 名是 DSA+。 Luminex 检测到的 DSA 患者的原发性无功能 (PNF)、移植物功能延迟、活检证实的急性排斥反应发生率较高,6 个月移植物存活率较低。免疫学和临床事件的联合终点在 DSA 患者中更为常见。结论。 Luminex 微球检测 DSA 与移植物功能障碍和免疫事件发生率显着升高相关。相反,Luminex 存在抗体但没有 DSA 则与良好的结果相关。在 AHG-CDC 交叉配型阴性的患者中,Luminex 检测到的低水平 DSA 可能有助于识别需要更积极的免疫监测或免疫抑制策略的患者。
Background. Sensitive techniques are able to detect low levels of circulating antibodies. For many newer techniques, the clinical consequences of these antibodies are unknown. We hoped to determine the significance of antibodies detected through the use of Luminex (R) microsphere-based assay.Methods. Patients who received kidney transplants between March 2003 and May 2004 with negative anti-human globulin-augmented complement-dependent cytotoxicity (AHG-CDC) crossmatches were retested for pre-transplant panel reactive antibodies (PRA) using Luminex microspheres and stored sera. Patients were considered to have circulating antibodies if either class I or class II Luminex PRA was >= 15%. These patients were then analysed for pre-transplant donor-specific antibodies (DSA). Clinical outcomes were compared in patients with and without DSAs.Results. Out of 136 patients who underwent transplantation, 55 had Luminex PRA >= 15%. Of these 55 patients, only 16 had a standard PRA >= 30% and 75% had a history of a sensitizing event. Twenty out of 55 patients were DSA+. Patients with DSA detected by Luminex had higher rates of primary non-function (PNF), delayed graft function, biopsy-proven acute rejection, and lower rates of graft survival at 6 months. A combined endpoint of immunological and clinical events was far more common in patients with DSA.Conclusion. The detection of DSAs by Luminex microspheres was associated with significantly higher rates of graft dysfunction and immunological events. Conversely, the presence of antibodies but no DSA by Luminex was associated with excellent outcomes. In patients with negative AHG-CDC crossmatches, the occurrence of low-level DSA by Luminex could assist in identifying patients that require more aggressive immune monitoring or immunosuppressive strategies.