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系统性红斑狼疮患者T细胞衰老与疾病活动度之间的关联。

Association between senescence of T cells and disease activity in patients with systemic lupus erythematosus.

作者信息

Kalim Handono, Wahono Cesarius Singgih, Permana Bunga Petriana Oktarini, Pratama Mirza Zaka, Handono Kusworini

机构信息

Rheumatology and Immunology Division, Department of Internal Medicine, Faculty of Medicine, Brawijaya University, Saiful Anwar General Hospital, Malang, Indonesia.

Department of Clinical Pathology, Faculty of Medicine, Brawijaya University, Saiful Anwar General Hospital, Malang, Indonesia.

出版信息

Reumatologia. 2021;59(5):292-301. doi: 10.5114/reum.2021.110318. Epub 2021 Oct 25.

Abstract

OBJECTIVES

Systemic lupus erythematosus (SLE) patients are predisposed to chronic immune activation, leading to accelerated immunosenescence. The aging of the immune system causes the T cells to express several senescence markers such as CD57 and KLRG1, which produce pro-inflammatory cytokine interferon γ (IFN-γ). Immunosenescence was associated with high morbidity and mortality in other diseases. This research was conducted to prove the association between senescent T cells and SLE disease activity.

MATERIAL AND METHODS

This research was an observational cross-sectional study on 53 women aged 16-45 years diagnosed with SLE based on SLICC 2012 criteria. All subjects were recorded for demographic and clinical data, and their SLE disease activity index (SLEDAI) score was measured to evaluate disease activity. Active disease was defined as SLEDAI score ≥ 3. The CD57 antigen and KLRG1 expression on CD4+ and CD8+ T cells were calculated from peripheral blood mononuclear cells (PBMC) by flow cytometry. Interferon γ was measured from serum using ELISA. The comparison was done using the Mann-Whitney U test, and correlation was tested using the Spearman test. Associations between variables were calculated using linear regression models.

RESULTS

Systemic lupus erythematosus patients with active disease had markedly higher CD4+KLRG1+ (3.1 [1.3-5.5]% vs. 0.3 [0.1-0.5]%), CD8+CD57+ (11.6 ±7.1% vs. 2.4 ±2.0%, = 0.000), and CD8+KLRG1+ T cell percentages (13.7 ±7.5% vs. 0.3 ±0.1%, = 0.000), and IFN- γ levels (208.9 [148.3-233.8] vs. 146.7 [130.2-210.8] pg/ml, = 0.048), compared to the inactive patients. Positive correlation and association was found between the CD8+CD57+ and CD8+KLRG1+ percentages with the SLEDAI score ( = 0.007 and = 0.007, for the linear regression analysis, respectively).

CONCLUSIONS

Systemic lupus erythematosus patients showed significantly higher senescence T cell markers compared to controls, and the increase of T cell senescence, especially in the CD8 compartment, has some association with increased disease activity in patients with SLE.

摘要

目的

系统性红斑狼疮(SLE)患者易发生慢性免疫激活,导致免疫衰老加速。免疫系统衰老会使T细胞表达多种衰老标志物,如CD57和KLRG1,这些标志物会产生促炎细胞因子干扰素γ(IFN-γ)。免疫衰老与其他疾病的高发病率和高死亡率相关。本研究旨在证实衰老T细胞与SLE疾病活动之间的关联。

材料与方法

本研究是一项观察性横断面研究,对53名年龄在16至45岁之间、根据2012年SLICC标准诊断为SLE的女性进行研究。记录所有受试者的人口统计学和临床数据,并测量其SLE疾病活动指数(SLEDAI)评分以评估疾病活动。疾病活动定义为SLEDAI评分≥3。通过流式细胞术从外周血单核细胞(PBMC)中计算CD4+和CD8+T细胞上的CD57抗原和KLRG1表达。使用酶联免疫吸附测定(ELISA)从血清中测量干扰素γ。采用曼-惠特尼U检验进行比较,使用斯皮尔曼检验进行相关性检验。使用线性回归模型计算变量之间的关联。

结果

与疾病非活动患者相比,疾病活动的系统性红斑狼疮患者的CD4+KLRG1+(3.1[1.3 - 5.5]%对0.3[0.1 - 0.5]%)、CD8+CD57+(11.6±7.1%对2.4±2.0%,P = 0.000)和CD8+KLRG1+T细胞百分比(13.7±7.5%对0.3±0.1%,P = 0.000)以及IFN-γ水平(208.9[148.3 - 233.8]对146.7[130.2 - 210.8]pg/ml,P = 0.048)显著更高。发现CD8+CD57+和CD8+KLRG1+百分比与SLEDAI评分之间存在正相关和关联(线性回归分析中,P分别为0.007和0.007)。

结论

与对照组相比,系统性红斑狼疮患者的衰老T细胞标志物显著更高,T细胞衰老的增加,尤其是在CD8亚群中,与SLE患者疾病活动增加存在一定关联。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aada/8609380/4fd6a1a36c6e/RU-59-45506-g001.jpg

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