Imperial College Kidney and Transplant Centre, The Hammersmith Hospital, London, UK.
Transplantation. 2013 Jan 27;95(2):341-6. doi: 10.1097/TP.0b013e3182743cfa.
BACKGROUND.: Donor-specific anti-HLA antibodies (DSA) are a major cause of alloimmune injury. Transplant recipients with negative complement-dependent cytotoxic crossmatch (CDC-XM) and donor cell-based flow cytometric crossmatch (flow-XM) but low level DSA (i.e., by Luminex) have worse outcomes compared with nonsensitized patients. The aim of this study was to establish whether complement-activating ability in this low-level DSA, present before transplantation, as determined by this technique is important in dictating pathogenicity. METHODS.: We retrospectively studied 52 patients with preformed DSA detected by single-antigen flow cytometric fluorescent beads (SAFBs). Patients were transplanted using a steroid-sparing regimen consisting of alemtuzumab induction, 1 week of corticosteroids and tacrolimus monotherapy.Fifteen (29%) of 52 patients experienced antibody-mediated rejection (AMR), whereas 37 (71%) patients did not. There were no demographic differences between patients with AMR and those without. Pretransplant sera were retested using a modified (SAFB) assay, which detects the presence of the complement fragment C4d as a result of DSA-induced complement activation. RESULTS.: C4d+DSA were detected in 10 (19%) of 52 patients. Biopsy-proven AMR occurred in 7 (70%) of the 10 patients with C4d+DSA and in 8 (19%) of 42 patients with C4d-DSA. AMR-free survival was worse in patients with C4d+DSA (P<0.001). CONCLUSIONS.: The ability of preformed, low-level, DSA to trigger C4d fixation in vitro in patients with negative conventional crossmatch tests is predictive for AMR. C4d SAFB is potentially a powerful tool for risk stratification prior to transplantation and may allow identification of unacceptable donor antigens, or patients who may require enhanced immunosuppression.
供体特异性抗 HLA 抗体（DSA）是同种免疫损伤的主要原因。与非致敏患者相比，具有阴性补体依赖性细胞毒性交叉匹配（CDC-XM）和基于供体细胞的流式细胞交叉匹配（flow-XM）但低水平 DSA（即通过 Luminex 检测）的移植受者的结局更差。本研究旨在确定移植前通过该技术确定的低水平 DSA （即通过 Luminex 检测）的补体激活能力是否对致病性有重要影响。方法：我们回顾性研究了 52 例通过单抗原流式细胞荧光珠（SAFB）检测到的预存 DSA 的患者。患者接受了包含阿仑单抗诱导、1 周皮质类固醇和他克莫司单药治疗的类固醇节约方案进行移植。52 例患者中有 15 例（29%）发生了抗体介导的排斥反应（AMR），而 37 例（71%）患者没有。AMR 患者与无 AMR 患者之间没有人口统计学差异。使用改良的（SAFB）检测法重新检测移植前血清，该检测法检测 DSA 诱导的补体激活导致的补体片段 C4d 的存在。结果：在 52 例患者中，有 10 例（19%）检测到 C4d+DSA。在 10 例 C4d+DSA 患者中有 7 例（70%）发生了活检证实的 AMR，在 42 例 C4d-DSA 患者中有 8 例（19%）发生了 AMR。C4d+DSA 患者的 AMR 无复发生存率更差（P<0.001）。结论：在常规交叉匹配试验阴性的患者中，预存的低水平 DSA 体外触发 C4d 固定的能力可预测 AMR。C4d SAFB 可能是移植前进行风险分层的有力工具，并可能有助于确定不可接受的供体抗原或可能需要增强免疫抑制的患者。
