在人类疱疹病毒 6 的影响下,长期 COVID 患者 NK 细胞细胞毒性和调节功能的变化(试验研究)。

IF 3.2 3区 医学 Q2 RHEUMATOLOGY
Rheumatology International Pub Date : 2024-12-01 Epub Date: 2024-09-30 DOI:10.1007/s00296-024-05677-3
Svitlana Zubchenko, Anna Havrylyuk, Iryna Kril, Olena Nadishko, Oleksandr Kolinkovskyi, Valentyna Chopyak
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引用次数: 0

摘要

长期的 COVID 常常伴有自身免疫紊乱。这种免疫系统失调的原因可能是 COVID-19 后患者体内 "迟钝的 "疱疹病毒感染重新活化。自身免疫的可能原因之一是在 HHV6 的影响下 NK 细胞的细胞毒性功能发生了变化。本研究的目的是研究轻度、中度和重度 COVID-19 后的长期 COVID 患者 NK 细胞上的受体配体 Fas-FasL、调节标记 CD38 和抑制受体 TIM-3 的表达情况,并确定这些患者形成自身免疫性疾病的风险因素。这项研究调查了 124 名年龄在 18 岁至 65 岁之间、患有长 COVID 的成年人(73 名女性和 51 名男性)。根据病史中 COVID-19 的轻度、中度和重度形式,以及有/无 HHV-6 再激活,对长期 COVID 患者进行了分组。对照组包括 20 名健康参与者。对所有患者进行了分子遗传学研究(PCR),以检测是否存在 DNA HHV6。多参数流式细胞术适用于 124 份从长期慢性阻塞性肺病患者和 20 名健康对照者处采集的 EDTA 外周血样本。结果表明,经过不同形式的 COVID-19 和 HHV-6 重新活化后,长 COVID 患者的急性抗病毒机制、导致组织损伤的反应和免疫病理(可能是自身免疫)之间出现了失衡。长COVID患者组中HHV-6的存在伴随着FasL和CD38的高表达,尤其是在病史中有严重COVID-19的患者中。与未感染 HHV-6 的患者相比,HHV-6 再激活患者体内 TIM-3 的减少使免疫耐受的维持面临 Th1 依赖性免疫反应的风险。HHV-6 再激活伴随着 FasL 和 CD38 的高表达,这表明 NK 细胞的过度激活、细胞毒性活性和随后的衰竭都在增加。这些患者的 NK 细胞失去了免疫调节能力,这为免疫病理(可能是自身免疫过程)的发展创造了先决条件。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Changes in the cytotoxic and regulatory functions of NK cells in patients with long-COVID under the influence of the human herpesvirus 6 (pilot study).

Long-COVID are often accompanied by the development of autoimmun disorders. Such dysregulation of the immune system can be caused by reactivation of "sluggish" herpesvirus infection in patients after COVID-19. The one of the possible causes of autoimmunization is a change in the cytotoxic functions of NK cells under the influence of HHV6. The aim of research was to study the expression of receptor-ligand Fas-FasL, regulating marker CD38 and inhibitory receptor TIM-3 on NK cells in patients with long-COVID after mild, moderate, and severe stage of COVID-19 in the anamnesis with or without reactivation of HHV-6 and to identify risk factors for the formation of autoimmune disorders in these patients. This study investigated 124 adults (73 female and 51 male) aged 18 to 65 years with long-COVID. The groups of patients with long-COVID were divided depending on mild, moderate, and severe forms of COVID-19 in the anamnesis and with/without reactivation of HHV-6. The control group included 20 healthy participants. Molecular genetic studies (PCR) were performed for all patients to detect the existence of DNA HHV6. Multiparametric flow cytometry was performed on 124 EDTA peripheral blood samples collected from long-COVID patients and 20 healthy controls. There was defined an imbalance between acute antiviral mechanisms, the response contributing to tissue damage and immunopathology, probably autoimmunity in patients with long-COVID after different forms of COVID-19 with reactivation of HHV-6. The presence of HHV-6 in groups with long-COVID was accompanied by higher expression of FasL and CD38, especially in patients, who had a severe form of COVID-19 in the anamnesis. The decrease in TIM-3 in patients with reactivation of HHV-6 compared to patients without HHV-6 puts the preservation of immunological tolerance at risk of Th1-dependent immune responses. The reactivation of HHV-6 is accompanied by higher expression of FasL and CD38, which indicates increased hyperactivation of NK cells, their cytotoxic activity, and subsequent exhaustion. NK cells of these patients lose their immunoregulatory ability, this creates prerequisites for the development of immunopathology, probably autoimmune processes.

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来源期刊
Rheumatology International
Rheumatology International 医学-风湿病学
CiteScore
7.30
自引率
5.00%
发文量
191
审稿时长
16. months
期刊介绍: RHEUMATOLOGY INTERNATIONAL is an independent journal reflecting world-wide progress in the research, diagnosis and treatment of the various rheumatic diseases. It is designed to serve researchers and clinicians in the field of rheumatology. RHEUMATOLOGY INTERNATIONAL will cover all modern trends in clinical research as well as in the management of rheumatic diseases. Special emphasis will be given to public health issues related to rheumatic diseases, applying rheumatology research to clinical practice, epidemiology of rheumatic diseases, diagnostic tests for rheumatic diseases, patient reported outcomes (PROs) in rheumatology and evidence on education of rheumatology. Contributions to these topics will appear in the form of original publications, short communications, editorials, and reviews. "Letters to the editor" will be welcome as an enhancement to discussion. Basic science research, including in vitro or animal studies, is discouraged to submit, as we will only review studies on humans with an epidemological or clinical perspective. Case reports without a proper review of the literatura (Case-based Reviews) will not be published. Every effort will be made to ensure speed of publication while maintaining a high standard of contents and production. Manuscripts submitted for publication must contain a statement to the effect that all human studies have been reviewed by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in an appropriate version of the 1964 Declaration of Helsinki. It should also be stated clearly in the text that all persons gave their informed consent prior to their inclusion in the study. Details that might disclose the identity of the subjects under study should be omitted.
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