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初发系统性红斑狼疮患者不同类型 CD4(+)叉头框蛋白 3(FoxP3)(+)T 细胞失衡。

Imbalance of different types of CD4(+) forkhead box protein 3 (FoxP3)(+) T cells in patients with new-onset systemic lupus erythematosus.

机构信息

Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, Department of Central Laboratory, The Second Part of First Hospital, Jilin University, Changchun, China.

出版信息

Clin Exp Immunol. 2013 Dec;174(3):345-55. doi: 10.1111/cei.12189.

Abstract

The aim of this study was to examine the numbers of CD4(+) CD25(-) forkhead box protein 3 (FoxP3)(+) , CD4(+) CD25(+) FoxP3(+) and CD4(+) CXCR5(+) FoxP3(+) T cells in patients with new-onset systemic lupus erythematosus (SLE). The numbers of CD4(+) CD25(-) FoxP3(+) , CD4(+) CD25(+) FoxP3(+) and CD4(+) CXCR5(+) FoxP3(+) T cells and the concentrations of serum interleukin (IL)-10 in 23 patients and 20 healthy controls (HC) were measured. The potential correlations between CD4(+) FoxP3(+) T cells, serum IL-10 and clinical measures in SLE patients were analysed. In comparison with that in the HC, significantly reduced numbers of CD4(+) CD25(+) FoxP3(+) and CD4(+) CXCR5(+) FoxP3(+) T cells, but increased numbers of CD4(+) CD25(-) FoxP3(+) T cells, were detected, accompanied by significantly lower levels of serum IL-10 in the patients. Stratification analysis indicated the numbers of CD4(+) CD25(+) FoxP3(+) and CD4(+) CXCR5(+) FoxP3(+) T cells and serum IL-10 levels in the patients with seropositive anti-dsDNA were significantly less than that in those with seronegative anti-dsDNA. Treatment with the anti-SLE therapy, particularly with prednisone, leflunomide and methotrexate, significantly improved the imbalance of these types of FoxP3(+) T cells and increased the concentrations of serum IL-10 in the drug-responding patients. The numbers of CD4(+) CD25(+) FoxP3(+) T cells were correlated negatively with the values of SLE disease activity index (SLEDAI), whereas the numbers of CD4(+) CD25(-) FoxP3(+) T cells were correlated positively with the values of SLEDAI, erythrocyte sedimentation rate (ESR) and serum C3. In addition, the concentrations of serum IL-10 were correlated positively with the numbers of CD4(+) CD25(+) FoxP3(+) T cells, but negatively with the values of SLEDAI, serum C3, CRP and ESR in these patients. Our data indicate that the imbalance of different types of FoxP3(+) CD4(+) T cells may contribute to the development of SLE in Chinese patients.

摘要

本研究旨在检测初诊系统性红斑狼疮(SLE)患者外周血中 CD4+CD25-FoxP3+、CD4+CD25+FoxP3+和 CD4+CXCR5+FoxP3+T 细胞的数量,并探讨其与临床指标的相关性。我们采用流式细胞术检测了 23 例 SLE 患者和 20 例健康对照者外周血 CD4+FoxP3+T 细胞、血清白介素(IL)-10 水平,分析了 SLE 患者外周血 CD4+FoxP3+T 细胞与血清 IL-10 水平及临床指标的相关性。结果显示,与健康对照者相比,SLE 患者外周血 CD4+CD25+FoxP3+和 CD4+CXCR5+FoxP3+T 细胞数量显著减少,而 CD4+CD25-FoxP3+T 细胞数量显著增加,血清 IL-10 水平明显降低。进一步分层分析发现,血清抗双链 DNA(dsDNA)抗体阳性的 SLE 患者外周血 CD4+CD25+FoxP3+和 CD4+CXCR5+FoxP3+T 细胞数量及血清 IL-10 水平明显低于抗体阴性者。经抗 SLE 治疗后,特别是应用泼尼松、来氟米特和甲氨蝶呤治疗后,药物有效组患者上述 FoxP3+T 细胞亚群失衡状态得到改善,血清 IL-10 水平升高。同时,SLE 患者外周血 CD4+CD25+FoxP3+T 细胞数量与 SLE 疾病活动指数(SLEDAI)评分呈负相关,而 CD4+CD25-FoxP3+T 细胞数量与 SLEDAI 评分、红细胞沉降率(ESR)和血清补体 3(C3)呈正相关。此外,血清 IL-10 水平与 CD4+CD25+FoxP3+T 细胞数量呈正相关,与 SLEDAI 评分、血清 C3、C 反应蛋白(CRP)和 ESR 呈负相关。本研究表明,不同类型 FoxP3+CD4+T 细胞亚群失衡可能与中国 SLE 患者的发病有关。

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