心脏移植中常规 C4d 免疫组化染色：长期结果。

Routine C4d immunohistochemistry in cardiac allografts: Long-term outcomes.

机构信息

Department of Pathology, The University of Chicago Medicine, Chicago, Illinois, USA.

出版信息

J Heart Lung Transplant. 2017 Dec;36(12):1329-1335. doi: 10.1016/j.healun.2017.09.004. Epub 2017 Sep 14.

DOI:10.1016/j.healun.2017.09.004

PMID:28988608

Abstract

BACKGROUND

In the past decade, C4d has emerged as a potential marker for antibody-mediated rejection (AMR); however, evidence on its use as a prognostic tool has been controversial. Although the International Society for Heart and Lung Transplantation guideline recommends early routine surveillance of C4d in heart transplantation, there is no consensus on its value in the pathologic assessment of AMR. Herein we present a correlation analysis of C4d immunoreactivity in endomyocardial biopsies with clinical cardiac dysfunction, cellular rejection, human leukocyte antigen (HLA) status, cardiac allograft vasculopathy (CAV) and death.

METHODS

A total of 5,840 endomyocardial biopsies from 296 heart transplant recipients (January 2004 to December 2014) were stained prospectively for C4d. Strong, diffuse endothelial staining was considered positive. All patients had at least 1 year of follow-up. Positive C4d staining was present in 53 biopsies from 28 patients. Sixteen of 28 patients had clinically significant cardiac dysfunction at the time of positive biopsy. In C4d-positive patients, the mean panel-reactive antibody (PRA) level was 33%. Ten patients demonstrated a first C4d positivity within the first year post-transplant, whereas 18 patients had C4d positivity after 1 year post-transplant. At autopsy, all 11 C4d-positive patients examined demonstrated cardiac allograft vasculopathy (CAV) as the underlying cause of death. In contrast, only 2 of 8 (25%) C4d-negative patients had CAV at autopsy. In the surviving cohort, there was an angiographic diagnosis of higher-than-moderate CAV in 10 patients (3.8%).

RESULTS

C4d-positive patients contributed to 67% of the overall institutional mortality in heart transplant recipients. Late C4d positivity (>1 year post-transplant) demonstrated an even higher risk for developing CAV and poor prognosis than early C4d positivity (within 1 year). In the C4d-negative group with postmortem examination, 75% (6 of 8) deaths were due to non-cardiac causes.

CONCLUSIONS

Our findings show a positive association of C4d with CAV and death. We identified a prognostic role for C4d in heart transplantation warranting routine long-term detection of this marker in the pathologic evaluation of cardiac AMR.

摘要

背景

在过去的十年中，C4d 已成为抗体介导排斥反应（AMR）的潜在标志物；然而，关于其作为预后工具的证据存在争议。尽管国际心肺移植学会指南建议在心脏移植中早期常规监测 C4d，但在 AMR 的病理评估中，其价值尚未达成共识。在此，我们报告了心肌活检中 C4d 免疫反应与临床心功能障碍、细胞排斥、人类白细胞抗原（HLA）状态、心脏移植物血管病（CAV）和死亡之间的相关性分析。

方法

对 296 例心脏移植受者（2004 年 1 月至 2014 年 12 月）的 5840 份心肌活检标本进行前瞻性 C4d 染色。强弥漫性内皮染色被认为是阳性。所有患者均有至少 1 年的随访。28 例患者的 53 份活检标本中存在阳性 C4d 染色。28 例患者中有 16 例在阳性活检时出现临床显著的心功能障碍。在 C4d 阳性患者中，平均 panel-reactive antibody（PRA）水平为 33%。10 例患者在移植后 1 年内首次出现 C4d 阳性，18 例患者在移植后 1 年出现 C4d 阳性。尸检时，所有 11 例 C4d 阳性患者均显示心脏移植物血管病（CAV）是死亡的根本原因。相比之下，尸检时 8 例 C4d 阴性患者中仅有 2 例（25%）存在 CAV。在存活队列中，10 例（3.8%）患者有更高程度的 CAV 的血管造影诊断。