Enhanced Diagnosis of Chronic Antibody-mediated Rejection Using Peritubular Capillary Multilayering.

IF 5 2区医学 Q1 IMMUNOLOGY

Transplantation Pub Date : 2025-10-09 DOI:10.1097/TP.0000000000005534

Brian J Nankivell, Meena Shingde, Chow Heok P'Ng, Thomas Tran

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Abstract

Background: Peritubular capillary multilayering (PTCML) of basement membranes is an ultrastructural feature of chronic antibody-mediated rejection (AMR) with uncertain diagnostic thresholds.

Methods: This single-center, prospective cohort study evaluated the relationships of PTCML with chronic AMR in 2541 kidney samples from 1195 recipients.

Results: Epidemiological modeling found that younger recipients, living donation, early AMR, pulse corticosteroid rejection treatment, later presentation, and higher donor-specific antibody strength were clinical risk factors for an abnormal PTCML score of ≥3. The total number of PTC layers was correlated with posttransplant time, AMR histology, donor-specific antibody positivity, renal dysfunction, proteinuria, and graft failure. Histological Banff cg, ptc, C4dptc, and C4dglom independently predicted PTCML ≥3. Mild PTCML of 3-4 layers with circumferential remodeling in multiple PTC showed 82.9% sensitivity and 72.7% specificity against the Banff cg≥1a reference test, verified using Banff 2022 AMR criteria, and considered "suspicious" for chronic AMR. PTCML ≥5 correlated with late graft failure. Normal PTC (n = 322) in early protocol samples showed 1 basement membrane layer, except for 12.5% with mild segmental reduplication involving 13.7 ± 10.2% capillary circumference. Circumferential scoring efficiently separated mild segmental PTCML from normal variability against pathological AMR multilayering. The poor 30.0% sensitivity and 91.1% specificity (n = 374 late indication biopsies, 2029 PTCs) of the Banff 2013 AMR criteria improved to 55.0% and 89.7% using modified PTCML ≥7 or 2×PTCML ≥5 criteria, which allowed for a diagnostic disease "rule-in."

Conclusions: Circumferential multilayering from PTCML ≥3 replicated across multiple capillaries optimally recognized mild chronic AMR as a superior histological marker of chronic tissue injury with high sensitivity. These ultrastructural diagnostic criteria for the detection of early chronic AMR phenotypes require multicenter validation.

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应用小管周围毛细血管多层造影增强慢性抗体介导排斥反应的诊断。

背景：基底膜小管周围毛细血管多层（PTCML）是慢性抗体介导的排斥反应（AMR）的超微结构特征，诊断阈值不确定。方法：这项单中心、前瞻性队列研究评估了来自1195名受者的2541个肾脏样本中PTCML与慢性AMR的关系。结果：流行病学模型发现，较年轻的受者、活体捐献、早期AMR、脉搏皮质类固醇排斥治疗、较晚出现、较高的供者特异性抗体强度是PTCML异常评分≥3的临床危险因素。PTC总层数与移植后时间、AMR组织学、供者特异性抗体阳性、肾功能障碍、蛋白尿和移植物衰竭相关。组织学Banff cg、ptc、C4dptc、C4dglom独立预测PTCML≥3。轻度PTCML 3-4层，多发PTC呈周向重塑，对Banff cg≥1a参考试验的敏感性为82.9%，特异性为72.7%，使用Banff 2022 AMR标准进行验证，考虑为慢性AMR“可疑”。PTCML≥5与晚期移植物衰竭相关。正常PTC （n = 322）在早期方案样本中显示1基膜层，除了12.5%有轻微的节段重复，包括13.7±10.2%的毛细血管周长。周向评分有效地将轻度节段性PTCML与病理性AMR多层的正常变异性分开。使用改进的PTCML≥7或2×PTCML≥5标准，Banff 2013 AMR标准的30.0%敏感性和91.1%特异性（n = 374例晚期指征活检，2029例ptc）改善至55.0%和89.7%，从而允许诊断疾病“规则化”。结论：PTCML≥3的周向多层复制跨越多个毛细血管，最佳地识别出轻度慢性AMR是一种高灵敏度的慢性组织损伤的优越组织学标志物。这些检测早期慢性AMR表型的超微结构诊断标准需要多中心验证。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Transplantation 医学-免疫学

CiteScore

8.50

自引率

11.30%

发文量

1906

审稿时长

1 months

期刊介绍： The official journal of The Transplantation Society, and the International Liver Transplantation Society, Transplantation is published monthly and is the most cited and influential journal in the field, with more than 25,000 citations per year. Transplantation has been the trusted source for extensive and timely coverage of the most important advances in transplantation for over 50 years. The Editors and Editorial Board are an international group of research and clinical leaders that includes many pioneers of the field, representing a diverse range of areas of expertise. This capable editorial team provides thoughtful and thorough peer review, and delivers rapid, careful and insightful editorial evaluation of all manuscripts submitted to the journal. Transplantation is committed to rapid review and publication. The journal remains competitive with a time to first decision of fewer than 21 days. Transplantation was the first in the field to offer CME credit to its peer reviewers for reviews completed. The journal publishes original research articles in original clinical science and original basic science. Short reports bring attention to research at the forefront of the field. Other areas covered include cell therapy and islet transplantation, immunobiology and genomics, and xenotransplantation.