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低水平供体特异性 HLA 抗体的 C4d 固定能力不能预测早期抗体介导的排斥反应。

C4d-fixing capability of low-level donor-specific HLA antibodies is not predictive for early antibody-mediated rejection.

机构信息

Transplantation Immunology and Nephrology, University Hospital Basel, Basel, Switzerland.

出版信息

Transplantation. 2010 Jun 27;89(12):1471-5. doi: 10.1097/TP.0b013e3181dc13e7.

Abstract

BACKGROUND

Recent studies indicate that not all low-level donor-specific human leukocyte antigen (HLA) antibodies (HLA-DSA) (i.e., positive by solid-phase assays, negative by complement-dependent cytotoxic-crossmatch) have a detrimental clinical impact. The aim of this study was to investigate whether the pretransplant C4d-fixing capability allows distinguishing harmful from presumably clinically irrelevant HLA-DSA.

METHODS

We retrospectively investigated 64 patients with low-level HLA-DSA detected by single-antigen flow beads (SAFB). Thirty-four of 64 patients (53%) experienced early antibody-mediated rejection (AMR), whereas 30 patients (47%) did not. HLA-DSA characteristics (i.e., number, class, and strength), frequency of retransplants, and immunosuppressive regimens were not different in these two groups. Pretransplant sera were reanalyzed using a modified SAFB assay measuring C4d fixation induced by HLA antibodies.

RESULTS

C4d-fixing HLA-DSA were observed in 11 of 64 patients (17%). AMR occurred in 6 of 11 patients (55%) with C4d-fixing HLA-DSA and in 28 of 53 patients (53%) without C4d-fixing HLA-DSA (P=1.0). Positive C4d staining in peritubular capillaries was detected in 6 of 11 patients (55%) with C4d-fixing HLA-DSA and in 21 of 53 patients (40%) without C4d-fixing HLA-DSA (P=0.50).

CONCLUSION

The pretransplant capability of low-level HLA-DSA to trigger C4d fixation in vitro is not predictive for early AMR or C4d deposition in peritubular capillaries in vivo. This argues against pretransplant C4d SAFB testing to define the clinical relevance of low-level HLA-DSA.

摘要

背景

最近的研究表明,并非所有低水平的供体特异性人类白细胞抗原(HLA)抗体(HLA-DSA)(即固相检测呈阳性,补体依赖性细胞毒性交叉配型检测呈阴性)都具有不良的临床影响。本研究旨在探讨移植前 C4d 固定能力是否能够区分有害和可能无临床意义的 HLA-DSA。

方法

我们回顾性研究了 64 例通过单抗原流珠(SAFB)检测到低水平 HLA-DSA 的患者。64 例患者中有 34 例(53%)发生早期抗体介导的排斥反应(AMR),而 30 例(47%)未发生。这两组患者的 HLA-DSA 特征(即数量、类别和强度)、再次移植频率和免疫抑制方案无差异。使用改良的 SAFB 检测,测量 HLA 抗体诱导的 C4d 固定,重新分析移植前的血清。

结果

在 64 例患者中,有 11 例(17%)观察到 C4d 固定的 HLA-DSA。在 11 例有 C4d 固定 HLA-DSA 的患者中,6 例(55%)发生 AMR,在 53 例无 C4d 固定 HLA-DSA 的患者中,28 例(53%)发生 AMR(P=1.0)。在有 C4d 固定 HLA-DSA 的 11 例患者中,有 6 例(55%)和 53 例无 C4d 固定 HLA-DSA 的患者中,有 21 例(40%)检测到肾小管周围毛细血管的 C4d 染色阳性(P=0.50)。

结论

移植前低水平 HLA-DSA 触发体外 C4d 固定的能力不能预测早期 AMR 或体内肾小管周围毛细血管的 C4d 沉积。这表明移植前 C4d SAFB 检测不能确定低水平 HLA-DSA 的临床意义。

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