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获得性再生障碍性贫血中干扰素-γ和穿孔素阳性 T 细胞:对治疗反应的影响。

Interferon-gamma and perforin-positive T cells in acquired aplastic anemia: implication in therapeutic response.

机构信息

Department of Hematology, All India Institute of Medical Sciences, New Delhi, India.

Department of Transplant Immunology and Immunogenetics, All India Institute of Medical Sciences, New Delhi, India.

出版信息

Clin Exp Immunol. 2022 May 12;207(3):272-278. doi: 10.1093/cei/uxab006.

Abstract

Acquired aplastic anemia (aAA) is an autoimmune disease, characterized by infiltration of T lymphocytes in the bone marrow with destruction of hematopoietic stem cells by the effector cells. Interferon-gamma (IFN-γ) and perforin are important mediators of cell destruction. In this flow cytometry-based study, we have investigated the percentage of intracellular IFN-γ+ and perforin+ CD5+ T cells in peripheral blood of newly diagnosed aAA patients before and after immunosuppressive therapy (IST). Patients were categorized as per standard disease severity and response to IST. The median percentage of IFN-γ+ and perforin+ CD5+ T cells was higher in untreated patients compared to healthy controls. The percentage of these cells was also increased in untreated severe and very severe aplastic anemia when compared with non-severe aplastic anemia patients. In patients before and after IST the median percentage of T cells producing IFN-γ and perforin was elevated in non-responders as compared to partial plus complete responders. The higher percentage of IFN-γ+ and perforin+ CD5+ T cells may be useful as an early diagnostic marker for aberrant activation of immune system and predict poor response to IST in aAA patients, who will benefit from alternative therapy.

摘要

获得性再生障碍性贫血(aAA)是一种自身免疫性疾病,其特征是骨髓中的 T 淋巴细胞浸润,并通过效应细胞破坏造血干细胞。干扰素-γ(IFN-γ)和穿孔素是细胞破坏的重要介质。在这项基于流式细胞术的研究中,我们研究了新诊断的 aAA 患者在免疫抑制治疗(IST)前后外周血中细胞内 IFN-γ+和穿孔素+ CD5+ T 细胞的百分比。根据标准疾病严重程度和 IST 反应对患者进行分类。与健康对照组相比,未经治疗的患者中 IFN-γ+和穿孔素+ CD5+ T 细胞的百分比更高。与非严重再生障碍性贫血患者相比,未经治疗的严重和极严重再生障碍性贫血患者中这些细胞的百分比也增加。在接受 IST 前后的患者中,与部分和完全缓解者相比,无反应者产生 IFN-γ 和穿孔素的 T 细胞的中位数百分比升高。IFN-γ+和穿孔素+ CD5+ T 细胞的较高百分比可能是免疫系统异常激活的早期诊断标志物,并可预测 aAA 患者对 IST 的反应不佳,这些患者将从替代治疗中受益。

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