肾移植受者 BK 病毒血症的基因组学研究。

Genomics of BK viremia in kidney transplant recipients.

机构信息

1 Montefiore-Einstein Center for Transplantation, Montefiore Medical Center, The University Hospital for Albert Einstein College of Medicine, Bronx, NY. 2 Renal Division, Montefiore Medical Center, The University Hospital for, Albert Einstein College of Medicine, Bronx, NY. 3 Department of Genetics, Division of Computational Genetics, Albert Einstein College of Medicine, Bronx, NY. 4 Address correspondence to: Enver Akalin, M.D., Montefiore Einstein Center for Transplantation, Montefiore Medical Center, The University Hospital for Albert Einstein College of Medicine, 111 East 210th Street, Bronx, NY 10467.

出版信息

Transplantation. 2014 Feb 27;97(4):451-6. doi: 10.1097/01.TP.0000437432.35227.3e.

DOI:10.1097/01.TP.0000437432.35227.3e

PMID:24310299

Abstract

BACKGROUND

This study aimed to investigate global gene expression profiles of BK viremia and nephropathy (BKVN) samples using microarrays to investigate the immunologic response to BK virus.

METHODS

Patients were monitored for BK viremia in the blood monthly for 6 months, then at 9 and 12 months after kidney transplantation. BKVN and normal transplant kidney biopsy samples, and whole blood samples of patients with and without BK viremia were analyzed by Affymetrix Human Gene 1.0 ST Arrays.

RESULTS

During a mean follow-up of 917±325 days, 61 of the 289 patients (21%) developed BK viremia at a median 149 (27, 1,113) days after transplantation with a median peak PCR titers of 35,900 (1,000, 2,677,000). The only significant risk factor for development of BK viremia was induction with anti-thymocyte globulin (P=0.03). Only four patients developed BKVN (1.3%). Pathogenesis-based transcript analysis revealed a significant increased expression of interferon-gamma and rejection induced (GRIT), quantitative cytotoxic T-cell (QCAT), quantitative constitutive and alternate macrophage, B-cell and natural killer cell-associated transcripts (NKAT), indicating an active inflammatory immune response in BKVN biopsies (n=3) compared to normal transplant kidney biopsies with (n=3) and without BK viremia (n=11). The whole blood gene expression profiles of 19 BK viremia patients revealed significant increased expression of GRIT, QCAT, and NKAT compared to 14 patients without viremia.

CONCLUSIONS

The results showed increased activity of cytotoxic T cells and natural killer cells in BKVN and viremia samples resembling acute rejection and suggested the involvement of both adaptive and innate immunity.

摘要

背景

本研究旨在通过微阵列分析研究 BK 病毒血症和肾病（BKVN）样本的全球基因表达谱，以研究针对 BK 病毒的免疫反应。

方法

患者在肾移植后每月监测血液中的 BK 病毒血症，持续 6 个月，然后在 9 个月和 12 个月时进行监测。使用 Affymetrix Human Gene 1.0 ST Arrays 分析 BKVN 和正常移植肾活检样本以及有和无 BK 病毒血症患者的全血样本。

结果

在平均 917±325 天的随访中，289 例患者中有 61 例（21%）在移植后中位数 149（27、1、113）天出现 BK 病毒血症，中位 PCR 滴度峰值为 35,900（1,000、2,677,000）。发生 BK 病毒血症的唯一显著危险因素是使用抗胸腺细胞球蛋白进行诱导（P=0.03）。只有 4 例患者发生 BKVN（1.3%）。基于发病机制的转录分析显示，干扰素-γ和排斥诱导（GRIT）、定量细胞毒性 T 细胞（QCAT）、定量固有和交替巨噬细胞、B 细胞和自然杀伤细胞相关转录物（NKAT）的表达显著增加，表明 BKVN 活检（n=3）与正常移植肾活检（n=3）和无 BK 病毒血症（n=11）相比，存在活跃的炎症免疫反应。19 例 BK 病毒血症患者的全血基因表达谱显示，与 14 例无病毒血症患者相比，GRIT、QCAT 和 NKAT 的表达显著增加。