1 Department of Transplant and Endocrine Surgery, Nagoya Daini Red Cross Hospital, Nagoya, Japan. 2 Department of Nephrology, Nagoya Daini Red Cross Hospital, Nagoya, Japan. 3 Department of Transplant Surgery, Masuko Memorial Hospital, Nagoya, Japan. 4 Department of Nephrology, Masuko Memorial Hospital, Nagoya, Japan. 5 Department of Renal Transplant Surgery, Aichi Medical University School of Medicine, Nagakute, Japan.
Transplantation. 2016 Oct;100(10):2194-202. doi: 10.1097/TP.0000000000001012.
It is unclear whether all donor-specific antibodies (DSA) can cause chronic antibody-mediated rejection (AMR). Subclinical stage before manifestation of renal dysfunction may be a critical period for reversing AMR. The aim of our study was to identify factors related to the development of subclinical AMR and to clarify the characteristics of de novo DSA.
Eight hundred ninety-nine renal transplants were screened for HLA antibody. De novo DSA were detected in 95 patients. Forty-three patients without renal dysfunction who underwent renal biopsies were enrolled in this study. Eighteen patients (41.9%) were diagnosed with biopsy-proven subclinical AMR and treated with plasmapheresis and rituximab-based therapy, whereas 25 showed no findings of AMR.
Significant subclinical AMR-related factors were younger recipients, history of acute T cell-mediated rejection and DSA class II, especially DR-associated DSA. Mean fluorescence intensity (MFI) values of DR-DSA were significantly higher, whereas DQ-DSA was not different between subclinical AMR and no AMR. The ΔMFI (>50%), DSA-MFI values greater than 3000, and C1q binding DSA were also significant subclinical AMR-related factors (P < 0.05). Among 18 patients treated for subclinical AMR, 8 patients (44.4%) obtained over 50% reduction of DSA-MFI and/or improvement or no deterioration of pathological findings. In contrast, 25 patients without subclinical AMR did not show renal dysfunction clinically. Moreover, all of the 8 patients with rebiopsy after 2 years continued to demonstrate no AMR.
About 40% of patients with de novo DSA demonstrated biopsy-proven subclinical AMR, leading to progressive graft injury. To validate the intervention and treatment for de novo DSA-positive patients without renal dysfunction, further study is necessary.
目前尚不清楚所有供体特异性抗体（DSA）是否都会导致慢性抗体介导的排斥反应（AMR）。肾功能障碍表现前的亚临床阶段可能是逆转 AMR 的关键时期。本研究旨在确定与亚临床 AMR 发展相关的因素，并阐明新出现的 DSA 的特征。
对 899 例肾移植患者进行 HLA 抗体筛查。在 95 例患者中检测到新出现的 DSA。对 43 例无肾功能障碍但接受肾活检的患者进行了本研究。其中 18 例（41.9%）患者被诊断为活检证实的亚临床 AMR，并接受了血浆置换和利妥昔单抗治疗，而 25 例患者未发现 AMR。
亚临床 AMR 相关的显著因素包括：受体年龄较小、急性 T 细胞介导排斥反应病史和 DSA Ⅱ类，特别是 DR 相关 DSA。DR-DSA 的平均荧光强度（MFI）值显著升高，而亚临床 AMR 与无 AMR 之间的 DQ-DSA 无差异。ΔMFI（>50%）、DSA-MFI 值大于 3000 和 C1q 结合 DSA 也是亚临床 AMR 相关的显著因素（P<0.05）。在接受亚临床 AMR 治疗的 18 例患者中，8 例（44.4%）患者的 DSA-MFI 值降低了 50%以上，或病理发现改善或无恶化。相比之下，25 例无亚临床 AMR 的患者在临床上没有肾功能障碍。此外，2 年后进行再次活检的 8 例患者均继续表现为无 AMR。
约 40%的新出现 DSA 患者表现为活检证实的亚临床 AMR，导致移植物进行性损伤。为了验证对无肾功能障碍的新出现 DSA 阳性患者的干预和治疗，还需要进一步的研究。
