Gibney Eric M, Cagle Linda R, Freed Brian, Warnell Stephanie E, Chan Larry, Wiseman Alexander C
Division of Nephrology, Hume-Lee Transplant Center, Virginia Commonwealth University, Richmond, VA, USA.
Nephrol Dial Transplant. 2006 Sep;21(9):2625-9. doi: 10.1093/ndt/gfl202. Epub 2006 Apr 27.
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 microsphere-based assay.
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 >or=15%. These patients were then analysed for pre-transplant donor-specific antibodies (DSA). Clinical outcomes were compared in patients with and without DSAs.
Out of 136 patients who underwent transplantation, 55 had Luminex PRA >or=15%. Of these 55 patients, only 16 had a standard PRA >or=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.
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.
敏感技术能够检测到低水平的循环抗体。对于许多新技术而言,这些抗体的临床后果尚不清楚。我们希望确定通过基于Luminex微球的检测方法所检测到的抗体的意义。
对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细胞毒性(AHG-CDC)交叉配型为阴性的患者,使用Luminex微球和储存的血清重新检测移植前群体反应性抗体(PRA)。如果I类或II类Luminex PRA≥15%,则认为这些患者存在循环抗体。然后对这些患者进行移植前供体特异性抗体(DSA)分析。比较有和没有DSA的患者的临床结局。
在136例接受移植的患者中,55例Luminex PRA≥15%。在这55例患者中,只有16例标准PRA≥30%,75%有致敏事件史。55例患者中有20例DSA阳性。通过Luminex检测到DSA的患者原发性无功能(PNF)、移植功能延迟、活检证实的急性排斥反应发生率较高,6个月时移植存活率较低。免疫和临床事件的综合终点在有DSA的患者中更为常见。
通过Luminex微球检测到DSA与移植功能障碍和免疫事件的发生率显著较高相关。相反,Luminex检测到有抗体但无DSA与良好的结局相关。在AHG-CDC交叉配型为阴性的患者中,Luminex检测到低水平DSA的发生有助于识别需要更积极免疫监测或免疫抑制策略的患者。