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系统性红斑狼疮中 T 细胞激活失调和细胞因子表达谱异常。

Dysregulated T Cell Activation and Aberrant Cytokine Expression Profile in Systemic Lupus Erythematosus.

机构信息

Clinical Research Center, The Affiliated Hospital of Guizhou Medical University, Guiyang 550004, China.

Guizhou Medical University, Guiyang 550004, China.

出版信息

Mediators Inflamm. 2019 Mar 17;2019:8450947. doi: 10.1155/2019/8450947. eCollection 2019.

Abstract

Accumulating evidence indicates a critical role for T cells and relevant cytokines in the pathogenesis of systemic lupus erythematosus (SLE). However, the specific contribution of T cells together with the related circulating cytokines in disease pathogenesis and organ involvement is still not clear. In the current study, we investigated relevant molecule expressions and cytokine levels in blood samples from 49 SLE patients and 22 healthy control subjects. The expression of HLA-DR and costimulatory molecules on T cells was evaluated by flow cytometry. Concentrations of serum C-reactive protein, erythrocyte sedimentation rate, anti-double-stranded DNA (anti-dsDNA) antibody, total lgG, complement 3, and complement 4 were measured. Serum cytokines and chemokines were measured by a cytometric bead array assay. Elevated frequencies of HLA-DR T cells and ICOS T cells were observed in SLE patients with positive anti-dsDNA antibodies compared with those in healthy controls ( < 0.001). The expression of HLA-DR T cells was positively correlated with SLEDAI ( = 0.15, < 0.01). Furthermore, levels of serum IL-6, MCP-1, TNFRI, IL-10, IL-12, and CCL20 were higher in SLE patients compared with healthy controls. In addition, patients with hematologic manifestations displayed elevated frequencies of HLA-DR T cells and ICOS T cells. Patients with renal manifestations had a decreased frequency of TIGIT T cells. These results suggested a dysregulated T cell activity and cytokine expression profiles in SLE subjects. We also developed a chemokine and cytokine profiling strategy to predict the activity of SLE, which has clinical implication for better monitoring the flares and remission during the course of SLE and for assessing therapeutic interventions.

摘要

越来越多的证据表明 T 细胞和相关细胞因子在系统性红斑狼疮(SLE)的发病机制中起着关键作用。然而,T 细胞在疾病发病机制和器官受累中的具体作用以及相关循环细胞因子仍不清楚。在本研究中,我们研究了 49 例 SLE 患者和 22 例健康对照者的血液样本中的相关分子表达和细胞因子水平。通过流式细胞术评估 T 细胞上 HLA-DR 和共刺激分子的表达。测量血清 C 反应蛋白、红细胞沉降率、抗双链 DNA(抗 dsDNA)抗体、总 IgG、补体 3 和补体 4 的浓度。通过细胞因子检测试剂盒检测血清细胞因子和趋化因子。与健康对照组相比,抗 dsDNA 抗体阳性的 SLE 患者 HLA-DR T 细胞和 ICOS T 细胞的频率升高(<0.001)。HLA-DR T 细胞的表达与 SLEDAI 呈正相关(=0.15,<0.01)。此外,SLE 患者的血清 IL-6、MCP-1、TNFRI、IL-10、IL-12 和 CCL20 水平高于健康对照组。此外,有血液学表现的患者 HLA-DR T 细胞和 ICOS T 细胞的频率升高。有肾脏表现的患者 TIGIT T 细胞的频率降低。这些结果表明 SLE 患者存在 T 细胞活性和细胞因子表达谱失调。我们还开发了一种趋化因子和细胞因子分析策略来预测 SLE 的活动,这对更好地监测 SLE 过程中的发作和缓解以及评估治疗干预具有临床意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d171/6441516/020264cf74c5/MI2019-8450947.001.jpg

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