肾移植后人类腺病毒感染的绝对淋巴细胞计数和人类腺病毒特异性 T 细胞免疫恢复。

Absolute lymphocyte count and human adenovirus-specific T-cell immune restoration of human adenovirus infection after kidney transplantation.

机构信息

Division of Infectious Diseases, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

Excellence Center of Organ Transplantation, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

出版信息

J Med Virol. 2019 Aug;91(8):1432-1439. doi: 10.1002/jmv.25468. Epub 2019 Apr 3.

DOI:10.1002/jmv.25468

PMID:30905076

Abstract

INTRODUCTION

Human adenovirus (HAdV) infection can cause substantial morbidity in kidney transplant (KT) recipients. Cell-mediated immunity plays an important role in controlling HAdV infection after KT.

METHODS

We prospectively (January 2015 to June 2018) investigated the absolute lymphocyte count (ALC) and interferon-γ-producing CD4 and CD8 T cells at diagnosis and at viral clearance by an intracellular cytokine assay after stimulating with HAdV whole lysate, hexon, and penton proteins. HAdV infection was defined as the presence of HAdV DNA load in plasma or clinical specimens measured by the polymerase chain reaction assay.

RESULTS

Eighteen adult KT recipients were diagnosed with HAdV infection at a median of 16 months (interquartile range [IQR], 2-39) after KT. The majority (94%) had HAdV-associated hemorrhagic cystitis. The median ALC at viral clearance was significantly higher compared with diagnosis (2257 cells/mm [IQR, 1544-3078] vs 1001 cells/mm [IQR, 641-1385]; P < 0.001). Eleven patients underwent measurement of the HAdV-specific T-cell response. The median numbers of CD4 and CD8 T cells at viral clearance were significantly higher compared with diagnosis (448 cells/mm [IQR, 248-651] vs 215 cells/mm [IQR, 159-272], P = 0.02; and 623 cells/mm [IQR, 242-772] vs 235 cells/mm [IQR, 129-266], P < 0.01), respectively. The median percentages of penton-specific CD4 and hexon-specific CD8 T cells at viral clearance were significantly higher compared with diagnosis (0.012% vs 0%, P = 0.03%; and 0.136% vs 0.016%, P = 0.003, respectively).

CONCLUSIONS

Our findings suggest a trend of ALC and HAdV-specific T-cell immune restoration in KT recipients who achieve successful HAdV clearance.

摘要

简介

人腺病毒（HAdV）感染可导致肾移植（KT）受者发生严重疾病。细胞介导的免疫在 KT 后控制 HAdV 感染中发挥重要作用。

方法

我们前瞻性地（2015 年 1 月至 2018 年 6 月）通过细胞内细胞因子测定，在用 HAdV 全裂解物、六邻体和五邻体蛋白刺激后，在诊断时和清除病毒时，检测了绝对淋巴细胞计数（ALC）和产生干扰素-γ的 CD4 和 CD8 T 细胞。通过聚合酶链反应检测 HAdV 载量，将 HAdV 感染定义为在血浆或临床标本中存在 HAdV DNA 负荷。

结果

18 例成人 KT 受者在 KT 后中位数为 16 个月（四分位距[IQR]，2-39）时被诊断为 HAdV 感染。大多数（94%）患者存在 HAdV 相关性出血性膀胱炎。与诊断时相比，病毒清除时的中位 ALC 明显升高（2257 个细胞/mm [IQR，1544-3078] vs 1001 个细胞/mm [IQR，641-1385]；P<0.001）。11 例患者接受了 HAdV 特异性 T 细胞反应的测量。与诊断时相比，病毒清除时的 CD4 和 CD8 T 细胞中位数明显升高（448 个细胞/mm [IQR，248-651] vs 215 个细胞/mm [IQR，159-272]，P=0.02；623 个细胞/mm [IQR，242-772] vs 235 个细胞/mm [IQR，129-266]，P<0.01）。与诊断时相比，病毒清除时的五邻体特异性 CD4 和六邻体特异性 CD8 T 细胞的中位数百分比明显升高（0.012%比 0%，P=0.03；0.136%比 0.016%，P=0.003）。