Sadaka Basma, Ejaz Nicole S, Shields Adele R, Cardi Michael A, Wadih George, Witte David, Abu Jawdeh Bassam G, Alloway Rita R, Woodle E Steve
1 Division of Nephrology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH. 2 Division of Transplantation, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH. 3 The Christ Hospital, Cincinnati, OH. 4 Department of Pathology, The Christ Hospital, Cincinnati, OH. 5 Department of Pathology, University of Cincinnati College of Medicine, Cincinnati, OH. 6 Department of Pathology, Cincinnati Children's Hospital, Cincinnati, OH.
Transplantation. 2015 Aug;99(8):1691-9. doi: 10.1097/TP.0000000000000694.
Histology remains a cornerstone for antibody-mediated rejection (AMR) diagnosis. Little data exist supporting histology for assessing therapeutic responses. This study evaluates histologic components in assessing AMR therapeutic responses.
Antibody-mediated rejection was diagnosed using Antibody Working Group criteria and Banff component scoring, and C4d staining data were analyzed. Statistics included independent and paired samples t test, χ(2), Fisher exact, or the Wilcoxon-signed rank test. Fifty-five AMR patients were analyzed. Early AMR was defined as occurring within 6 months after transplantation and treated with a single rituximab dose and 4 bortezomib doses preceded by plasmapheresis. Allograft biopsies were performed within 48 hours of treatment; repeat biopsy was performed 14 to 21 days later.
Early AMR demonstrated histologic improvement in mean scores for acute Banff components glomerulitis (g), C4d, g+ peritubular capillaritis (ptc) and acute composite score, but showed deterioration in chronic Banff components tubular atrophy and interstitial fibrosis. Late AMR showed improved mean scores for acute Banff components tubulitis, interstitial inflammation, g, ptc, g + ptc, C4d, and acute composite score, but chronic scores did not change. Significant changes in distribution of Banff scores after treatment were observed for g, C4d, tubular atrophy, and interstitial fibrosis scores in early AMR patients and tubulitis, interstitial inflammation, g, ptc, and C4d in late AMR.
These results show that: (1) Banff component scoring provides insights into histologic responses to AMR therapy and may provide a potential endpoint for clinical AMR trials. (2) Early and late AMR demonstrate differences in acute and chronic Banff components at the time of the AMR diagnostic biopsy, as well as differential responses to AMR therapy.
组织学仍然是抗体介导性排斥反应（AMR）诊断的基石。支持组织学用于评估治疗反应的数据很少。本研究评估组织学成分在评估AMR治疗反应中的作用。
采用抗体工作组标准和班夫成分评分诊断抗体介导性排斥反应，并分析C4d染色数据。统计学方法包括独立样本和配对样本t检验、χ²检验、Fisher精确检验或Wilcoxon符号秩检验。对55例AMR患者进行分析。早期AMR定义为移植后6个月内发生，采用单次利妥昔单抗剂量和4次硼替佐米剂量治疗，治疗前进行血浆置换。在治疗后48小时内进行移植肾活检；14至21天后进行重复活检。
早期AMR在急性班夫成分肾小球炎（g）、C4d、g+肾小管周围毛细血管炎（ptc）和急性综合评分的平均得分上显示出组织学改善，但在慢性班夫成分肾小管萎缩和间质纤维化方面显示出恶化。晚期AMR在急性班夫成分肾小管炎、间质炎症、g、ptc、g + ptc、C4d和急性综合评分的平均得分上显示出改善，但慢性评分未改变。在早期AMR患者中，g、C4d、肾小管萎缩和间质纤维化评分以及晚期AMR中的肾小管炎、间质炎症、g、ptc和C4d评分在治疗后班夫评分分布有显著变化。
这些结果表明：（1）班夫成分评分可深入了解AMR治疗的组织学反应，并可能为临床AMR试验提供潜在的终点。（2）早期和晚期AMR在AMR诊断性活检时的急性和慢性班夫成分存在差异，以及对AMR治疗的反应也不同。
