Kidney Transplant Service, Department of Medicine, University of California San Francisco (UCSF), San Francisco, CA, USA.
Immunogenetics and Transplantation Laboratory, Department of Surgery, University of California San Francisco (UCSF), San Francisco, CA, USA.
Ann Transplant. 2021 Dec 1;26:e934175. doi: 10.12659/AOT.934175.
BACKGROUND Solid-phase assays to investigate the complement-activating capacity of HLA antibodies have been utilized to optimize organ allocation and improve transplant outcomes. The clinical utility of C1q/C3d-binding characteristics of de novo donor-specific anti-HLA antibodies (dnDSA) associated with C4d-positive antibody-mediated rejection (C4d⁺ AMR) in kidney transplants (KTx) has not been defined. MATERIAL AND METHODS Sera from 120 KTx recipients that had dnDSA concurrent with protocol/cause biopsy (median 3.8 years after transplantation) were screened for C1q and C3d-binding dnDSA. The difference in the incidence of C4d⁺ AMR between recipients with and without C1q/C3d-binding dnDSA was assessed. RESULTS Over 86% of dnDSAs were class II antibodies. The immunodominant dnDSAs characterized by the highest median fluorescence intensity (MFI) in most recipients were HLA-DQ antibodies (67%). Most recipients (62%, n=74) had either C1q⁺ (56%), C3d⁺ (48%), or both C1q⁺C3d⁺ (41.2%) dnDSA, while the remaining 38% were negative for both C1q and C3d. Of those with C1q⁺/C3d⁺ dnDSA, 87% had high-MFI IgG (MFI=14144±5363 and 13932±5278, respectively), while 65% of C1q⁻C3d⁻ dnDSA had low-MFI IgG (MFI=5970±3347). The incidence of C4d+ AMR was significantly higher in recipients with C1q⁺ (66%), C3d+ (74%), and C1q⁺C3d⁺ (72%) dnDSA than in those with C1q⁻C3d⁻ dnDSA (30%) recipients. Recipients with C3d⁺/C1q⁺ dnDSA had higher C4d⁺ scores on biopsy. CONCLUSIONS C1q⁺/C3d⁺ dnDSA were associated with C4d⁺ AMR and high-IgG MFI. Our data call into question the predictive utility of C1q/C3d-binding assays in identifying KTx recipients at risk of allograft failure. In conclusion, IgG MFI is sufficient for clinical management, and the C1q/C3d-assays with added cost do not provide any additional information.
用于研究 HLA 抗体补体激活能力的固相测定法已被用于优化器官分配并改善移植结果。在肾移植（KTx）中，与 C4d 阳性抗体介导的排斥反应（C4d⁺ AMR）相关的新出现的供体特异性抗 HLA 抗体（dnDSA）的 C1q/C3d 结合特征的临床实用性尚未确定。
对 120 名接受 KTx 且在移植后 3.8 年进行方案/原因活检时同时存在 dnDSA 的患者的血清进行 C1q 和 C3d 结合 dnDSA 的筛选。评估具有和不具有 C1q/C3d 结合 dnDSA 的患者发生 C4d⁺ AMR 的发生率差异。
超过 86%的 dnDSAs 为 II 类抗体。在大多数患者中，免疫显性 dnDSAs 的特征是最高中位荧光强度（MFI），其中 HLA-DQ 抗体（67%）最为突出。大多数患者（62%，n=74）存在 C1q⁺（56%）、C3d⁺（48%）或 C1q⁺C3d⁺（41.2%）dnDSA，而其余 38%的患者 C1q 和 C3d 均为阴性。在 C1q⁺/C3d⁺ dnDSA 患者中，87%的 IgG 具有高 MFI（MFI=14144±5363 和 13932±5278），而 65%的 C1q⁻C3d⁻ dnDSA 的 IgG 具有低 MFI（MFI=5970±3347）。在 C1q⁺（66%）、C3d⁺（74%）和 C1q⁺C3d⁺（72%）dnDSA 的患者中，C4d+ AMR 的发生率明显高于 C1q⁻C3d⁻ dnDSA（30%）的患者。在具有 C3d⁺/C1q⁺ dnDSA 的患者中，活检时 C4d+的评分更高。
C1q⁺/C3d⁺ dnDSA 与 C4d⁺ AMR 和高 IgG MFI 相关。我们的数据对 C1q/C3d 结合测定法在识别移植失败风险的同种异体移植物的预测实用性提出了质疑。总之，IgG MFI 足以用于临床管理，并且具有附加成本的 C1q/C3d 测定法没有提供任何其他信息。
