Department of Pathology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Transplantation. 2013 Jan 15;95(1):128-36. doi: 10.1097/TP.0b013e3182777f28.
Subclinical antibody-mediated allograft rejection (AMR) has been characterized in serial biopsies from presensitized recipients but has not been systematically studied in conventional renal transplants.
We evaluated 1101 consecutive kidney transplant biopsies (400 surveillance biopsies [SBx] and 701 for cause biopsies [FCBx]) with concurrent donor-specific antibody (DSA) studies, C4d staining, and ultrastructural examination.
A comparison of AMR-related features (DSA and DSA class, C4d staining, and microvascular injury) demonstrated that these were qualitatively and quantitatively associated with each other and with graft dysfunction. A major difference between SBx and FCBx was that the complete AMR phenotype was more common in FCBx. Among SBx, 8.5% showed complete or incomplete AMR with predominance of an incomplete phenotype (according to the Banff schema, these were acute AMR [23.5%], chronic active AMR [14.7%], suspicious for acute AMR [41.1%], suspicious for chronic active AMR [2.9%], and only microvascular injury insufficient to consider AMR [17.5%]). Persistence or worsening of AMR in a subsequent biopsy occurred in 38.2% of cases independently of the strength of AMR findings in the first biopsy (e.g., progression to chronic AMR occurred also in cases with suspicious or nondiagnostic findings). Temporal progression from subclinical to clinically evident AMR is consistent with the fact that, overall, the biopsies with incomplete phenotype (DSA±C4d) occurred between 14.52 and 20.86 months, whereas the complete phenotype occurred much later (36.71 months).
An accurate diagnostic interpretation of the potentially important but incomplete, subclinical, AMR phenotype represents a serious challenge that may impact clinical management.
在致敏受者的连续活检中已经描述了亚临床抗体介导的同种异体移植排斥反应（AMR），但尚未在常规肾移植中进行系统研究。
我们评估了 1101 例连续的肾移植活检（400 例监测活检 [SBx] 和 701 例因原因活检 [FCBx]），同时进行了供体特异性抗体（DSA）研究、C4d 染色和超微结构检查。
对 AMR 相关特征（DSA 和 DSA 类别、C4d 染色和微血管损伤）的比较表明，这些特征在质量和数量上彼此相关，与移植物功能障碍相关。SBx 和 FCBx 之间的一个主要区别是，在 FCBx 中更常见完全或不完全的 AMR 表型。在 SBx 中，8.5%显示完全或不完全 AMR，以不完全表型为主（根据 Banff 方案，这些是急性 AMR[23.5%]、慢性活动性 AMR[14.7%]、疑似急性 AMR[41.1%]、疑似慢性活动性 AMR[2.9%]和仅微血管损伤不足以考虑 AMR[17.5%]）。在随后的活检中，38.2%的病例中 AMR 持续或恶化，与第一次活检中 AMR 发现的强度无关（例如，在可疑或非诊断性发现的情况下，也会发生慢性 AMR 的进展）。从亚临床到临床明显 AMR 的时间进展与事实一致，即总体而言，不完全表型（DSA±C4d）的活检发生在 14.52 至 20.86 个月之间，而完全表型发生得晚得多（36.71 个月）。
对潜在重要但不完全、亚临床的 AMR 表型进行准确的诊断解释是一个严峻的挑战，可能会影响临床管理。
