在儿童肠移植后急性细胞排斥反应和其他肠炎期间，单核细胞唾液酸黏附分子表达增加。

Increased monocyte expression of sialoadhesin during acute cellular rejection and other enteritides after intestine transplantation in children.

机构信息

Hillman Center for Pediatric Transplantation, Children's Hospital of Pittsburgh, and the University of Pittsburgh, Pittsburgh, PA, USA.

出版信息

Transplantation. 2012 Mar 15;93(5):561-4. doi: 10.1097/TP.0b013e3182449189.

DOI:10.1097/TP.0b013e3182449189

PMID:22249367

Abstract

BACKGROUND

Sialoadhesin (CD169) facilitates T-cell priming when overexpressed on inflammatory monocytes. Monocyte-derived macrophages prime acute cellular rejection after intestine transplantation (ITx).The purpose of this study was to evaluate whether CD169-expressing activated monocytes associate with or predict ITx rejection.

METHODS

After informed consent (ClinicalTrials.gov NCT No. 01163578), activated CD169+CD14+monocytes were measured by flow cytometry in five normal healthy adult volunteers (group A), and 56 children with ITx sampled cross-sectionally (group B, 26), longitudinally (group C, 18), or during infection/inflammation without rejection (group D: acute enteritis, 9; Helicobacter pylori, 1; Streptococcal pharyngitis 1; and posttransplant lymphoma, 1). Activated monocytes were tested for correlations with donor-specific alloreactivity in simultaneous mixed lymphocyte co-cultures.

RESULTS

Median age was 3 years (range 0.5-21 yr), and distribution of ITx-alone:combined liver-ITx was 25:31. Higher frequencies (%) of activated monocytes were seen during rejection in group B and infection/inflammation without rejection in group D (58 ± 28 and 73 ± 26), compared with nonrejectors or normal controls (10.6 ± 7.9 or 10.7 ± 6.5, P=0.001). In longitudinal monitoring, rejectors also showed higher activated monocyte frequencies (%) before ITx (64 ± 26 vs. 13.4 ± 8.6, P=0.0007) and during acute cellular rejection (55 ± 28 vs. 22.4 ± 15, P=0.006) when compared with nonrejectors. Activated monocytes correlated significantly with allospecific CD154+T-cytotoxic memory cells (Spearman r=0.688, P=7.1E-05) and CD154+B cells (r=0.518, P=0.005) in ITx recipients without inflammation/infection but not in group D.

CONCLUSIONS

Monocytes overexpress sialoadhesin nonspecifically during ITx rejection and systemic or enteritic inflammatory states. When combined with allospecific T and B cells, this information may differentiate between rejection and other enteritides.

摘要

背景

唾液酸结合蛋白（CD169）在炎症性单核细胞中过表达时，有助于 T 细胞的初始激活。单核细胞衍生的巨噬细胞在肠移植（ITx）后引发急性细胞排斥反应。本研究的目的是评估表达 CD169 的激活单核细胞是否与 ITx 排斥反应相关或可预测其发生。

方法

在获得知情同意（ClinicalTrials.gov 注册号：01163578）后，通过流式细胞术测量了五名正常健康成年志愿者（A 组）中激活的 CD169+CD14+单核细胞，以及 56 名 ITx 患儿的横断面（B 组，26 名）、纵向（C 组，18 名）或感染/炎症无排斥（D 组：急性肠炎 9 名；幽门螺杆菌 1 名；链球菌咽炎 1 名；移植后淋巴瘤 1 名）样本。同时在混合淋巴细胞共培养中检测激活单核细胞与供者特异性同种反应性的相关性。

结果

中位年龄为 3 岁（范围 0.5-21 岁），ITx 单器官移植与肝-ITx 联合移植的比例为 25:31。与非排斥者或正常对照组（10.6±7.9 或 10.7±6.5）相比，B 组排斥者和 D 组感染/炎症无排斥者的激活单核细胞频率（%）更高（58±28 和 73±26）。在纵向监测中，与非排斥者相比，排斥者在 ITx 前（64±26 与 13.4±8.6，P=0.0007）和急性细胞排斥时（55±28 与 22.4±15，P=0.006）的激活单核细胞频率（%）也更高。与无炎症/感染的 ITx 受者相比，激活的单核细胞与同种反应性 CD154+B 细胞（r=0.518，P=0.005）和 CD154+T 细胞记忆细胞（r=0.688，P=7.1E-05）显著相关，但与 D 组无相关性。