Department of Urology, Tokyo Women's Medical University, Tokyo, Japan; Department of Transplant Surgery, Shonan Kamakaura General Hospital, Kanagawa, Japan.
Department of Urology, Tokyo Women's Medical University, Tokyo, Japan.
Transpl Immunol. 2019 Dec;57:101230. doi: 10.1016/j.trim.2019.101230. Epub 2019 Aug 6.
The occurrence of acute antibody-mediated rejection (ABMR) is higher in flow cytometric crossmatch (FCXM)-positive patients despite desensitization. Accumulating evidence suggests a correlation between the complement-binding ability of donor-specific antibodies (DSAs) and the risk of ABMR. Here, we investigated the correlation between complement C3d-fixing ability of preformed DSA and ABMR risk, the efficacy of a desensitization protocol for patients with C3d-fixing DSA, and the risk of ABMR in 21 DSA- and FCXM-positive patients. We retrospectively analyzed the C3d-fixing ability and mean fluorescence intensity (MFI) of preformed DSA before and after desensitization. Six patients had non-C3d-fixing DSA and 15 had C3d-fixing DSA. The presence of C3d-fixing DSA before desensitization was correlated with the incidence of acute ABMR within 1 year after transplantation (p = .04) and chronic ABMR (p = .03). Moreover, the MFI of preformed DSA differed between responder and non-responder C3d-fixing DSA after desensitization (p < .0001). The C3d-fixing ability of preformed DSA with low MFI disappeared after desensitization. These results indicate that measuring DSA C3d-fixing ability may identify patients with a high risk of ABMR, especially before desensitization. CLINICAL TRIAL NOTATION: UMIN Clinical Trials Registry (UMIN-CTR) number: UMIN000033449.
尽管进行了脱敏治疗，流式细胞交叉配型（FCXM）阳性患者发生急性抗体介导的排斥反应（ABMR）的几率仍然较高。越来越多的证据表明，供体特异性抗体（DSA）的补体结合能力与 ABMR 风险之间存在相关性。在这里，我们研究了预先形成的 DSA 补体 C3d 固定能力与 ABMR 风险之间的相关性、针对 C3d 固定 DSA 患者的脱敏方案的疗效，以及 21 例 DSA 和 FCXM 阳性患者的 ABMR 风险。我们回顾性分析了脱敏前后预先形成的 DSA 的 C3d 固定能力和平均荧光强度（MFI）。6 例患者存在非 C3d 固定 DSA，15 例患者存在 C3d 固定 DSA。脱敏前存在 C3d 固定 DSA 与移植后 1 年内急性 ABMR（p=0.04）和慢性 ABMR（p=0.03）的发生率相关。此外，脱敏后 C3d 固定 DSA 的预形成 DSA 的 MFI 存在应答者和非应答者之间的差异（p<0.0001）。低 MFI 的预形成 DSA 的 C3d 固定能力在脱敏后消失。这些结果表明，测量 DSA C3d 固定能力可能会识别出 ABMR 风险较高的患者，尤其是在脱敏之前。临床试验注册号：UMIN 临床研究注册（UMIN-CTR）编号：UMIN000033449。
