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水痘带状疱疹病毒介导的急性视网膜坏死患者房水中T淋巴细胞和细胞因子的流式细胞术分析

Flow cytometric analysis of T lymphocytes and cytokines in aqueous humor of patients with varicella zoster virus-mediated acute retinal necrosis.

作者信息

Kang Hao, Wei Yunbo, Liu Ming, Yu Di, Tao Yong

机构信息

Department of Ophthalmology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.

Laboratory of Immunology for Environment and Health, Shandong Analysis and Test Center, Qilu University of Technology (Shandong Academy of Sciences), Jinan, Shandong, China.

出版信息

BMC Ophthalmol. 2021 May 1;21(1):193. doi: 10.1186/s12886-021-01951-1.

Abstract

BACKGROUND

The purpose of this study is to investigate the aqueous humor (AH) T lymphocyte subsets and cytokines of acute retinal necrosis (ARN) to elucidate the immunologic inflammatory features of this disorder.

METHODS

Three patients with ARN infected with varicella zoster virus (VZV) who underwent multiple intravitreal injections of ganciclovir were enrolled in this study. The control group consisted of four non-infectious patients with acute anterior uveitis (AAU). Flow cytometric analysis was performed on the lymphocyte subsets from the AH and peripheral blood (PB) samples during the active phase of intraocular inflammation. Five inflammatory cytokines were measured in each AH sample and various clinical characteristics were also assessed.

RESULTS

VZV deoxyribonucleic acid (DNA) was detected by real-time polymerase chain reaction (PCR) in AH from all the ARN patients, who showed higher CD8+ T lymphocytes population in AH than the AAU patients (p = 0.006). CD4/CD8 ratios of T lymphocytes and the percentage of CD8 + CD25+ T lymphocytes in AH were significantly lower in ARN than in AAU (p = 0.006; p = 0.012). In the ARN patients, the percentages of CD4+ and CD8+ T lymphocytes in AH were higher than those found in PB. The percentage of CD4 + CD25+ T lymphocytes in AH was significantly higher than the proportion in PB in the AAU patients (p = 0.001). Immunoregulatory cytokine Interleukin-10 in AH was significantly elevated in the ARN patients in comparison with the case of the AAU patients (p = 0.036). In ARN, the copy number of VZV DNA in AH positively correlated with the percentage of CD8+ T lymphocytes in AH and negatively correlated with the CD4/CD8 ratio in AH during the course of disease treatment (p = 0.009, r = 0.92; p = 0.039, r = - 0.834).

CONCLUSION

The ARN patients caused by VZV had different intraocular T lymphocyte subsets and cytokines profile than those of the non-infectious patients. High percentages of CD8+ T lymphocytes and low CD4/CD8 T cell ratios may be a potential biomarker for diagnosis of viral-infectious uveitis. T lymphocytes examination at the inflammatory sites has the potential to become a useful research tool for differentiating viral and non-viral uveitis.

摘要

背景

本研究旨在调查急性视网膜坏死(ARN)患者房水中的T淋巴细胞亚群及细胞因子,以阐明该疾病的免疫炎症特征。

方法

本研究纳入了3例感染水痘带状疱疹病毒(VZV)并接受多次玻璃体内注射更昔洛韦的ARN患者。对照组由4例非感染性急性前葡萄膜炎(AAU)患者组成。在眼内炎症活动期,对房水和外周血(PB)样本中的淋巴细胞亚群进行流式细胞术分析。检测每个房水样本中的5种炎性细胞因子,并评估各种临床特征。

结果

通过实时聚合酶链反应(PCR)在所有ARN患者的房水中检测到VZV脱氧核糖核酸(DNA),这些患者房水中的CD8+T淋巴细胞数量高于AAU患者(p = 0.006)。ARN患者房水中T淋巴细胞的CD4/CD8比值及CD8+CD25+T淋巴细胞百分比显著低于AAU患者(p = 0.006;p = 0.012)。在ARN患者中,房水中CD4+和CD8+T淋巴细胞百分比高于外周血中的百分比。AAU患者房水中CD4+CD25+T淋巴细胞百分比显著高于外周血中的比例(p = 0.001)。与AAU患者相比,ARN患者房水中免疫调节细胞因子白细胞介素-10显著升高(p = 0.036)。在疾病治疗过程中,ARN患者房水中VZV DNA拷贝数与房水中CD8+T淋巴细胞百分比呈正相关,与房水中CD4/CD8比值呈负相关(p = 0.009,r = 0.92;p = 0.039,r = -0.834)。

结论

由VZV引起的ARN患者与非感染性患者的眼内T淋巴细胞亚群及细胞因子谱不同。高比例的CD8+T淋巴细胞和低CD4/CD8 T细胞比值可能是诊断病毒性感染性葡萄膜炎的潜在生物标志物。在炎症部位进行T淋巴细胞检测有可能成为区分病毒性和非病毒性葡萄膜炎的有用研究工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe41/8088617/214acb124b67/12886_2021_1951_Fig1_HTML.jpg

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