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系统性红斑狼疮患者外周血B淋巴细胞中细胞型FLICE抑制蛋白的上调与临床特征相关。

Up-regulation of cellular FLICE-inhibitory protein in peripheral blood B lymphocytes in patients with systemic lupus erythematosus is associated with clinical characteristics.

作者信息

Tao J, Dong J, Li Y, Liu Y-Q, Yang J, Wu Y, Li L, Shen G-X, Tan Z-J, Tu Y-T

机构信息

Department of Dermatology, Affiliated Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

出版信息

J Eur Acad Dermatol Venereol. 2009 Apr;23(4):433-7. doi: 10.1111/j.1468-3083.2009.03095.x.

Abstract

BACKGROUND

Systemic lupus erythematosus (SLE) is an autoimmune disease which is involved in T- and B-lymphocyte-mediated autoimmunity. Apoptosis contributes to the maintenance of lymphocytes homeostasis and the deletion of autoreactive cells in SLE. Although there is evidence that cellular FLICE-inhibitory protein (c-FLIP), an antiapoptosis protein, is increased in human lupus T cells to keep them from apoptosis, but the expression of apoptosis-regulatory protein c-FLIP in SLE B lymphocytes remains unknown.

AIMS

To study the expression of c-FLIP in peripheral blood B lymphocytes in SLE patients and to investigate the relationship among the expression of c-FLIP in peripheral blood B lymphocytes in SLE patients, clinical manifestation and the levels of interleukin-4 (IL-4) and IL-10.

METHODS

In this study, we detected the expression of c-FLIP in peripheral blood B lymphocytes in SLE patients by flow cytometry and the levels of IL-4 and IL-10 in SLE serum samples by enzyme-linked immunosorbent assay and analysed their relationship with clinical characteristics.

RESULTS

We observed a significantly higher percentage of c-FLIP in peripheral B cells in SLE patients with active disease when compared to inactive ones and healthy controls. And the expression of c-FLIP in lupus peripheral B cells showed positive correlations with SLEDAI, erythrocyte sedimentation rate, C-reactive protein, antinucleosome antibody titre, IL-4, and IL-10, and negative correlation with white blood cell count. Patients with lupus nephritis had higher levels of c-FLIP in peripheral B cells than patients without lupus nephritis.

CONCLUSION

Our data show that overexpression of c-FLIP is relevant to the activity and severity of SLE. Its overexpression might play a role in preventing B cell from apoptosis in SLE. The cause of c-FLIP overexpression may be due to the increase of IL-4 and IL-10 levels in SLE patients.

摘要

背景

系统性红斑狼疮(SLE)是一种自身免疫性疾病,涉及T淋巴细胞和B淋巴细胞介导的自身免疫。细胞凋亡有助于维持淋巴细胞的稳态以及清除SLE中的自身反应性细胞。尽管有证据表明抗凋亡蛋白细胞型FLICE抑制蛋白(c-FLIP)在人类狼疮T细胞中增加,以防止其凋亡,但凋亡调节蛋白c-FLIP在SLE B淋巴细胞中的表达仍不清楚。

目的

研究c-FLIP在SLE患者外周血B淋巴细胞中的表达,并探讨SLE患者外周血B淋巴细胞中c-FLIP的表达、临床表现以及白细胞介素-4(IL-4)和IL-10水平之间的关系。

方法

在本研究中,我们通过流式细胞术检测SLE患者外周血B淋巴细胞中c-FLIP的表达,并通过酶联免疫吸附测定法检测SLE血清样本中IL-4和IL-10的水平,并分析它们与临床特征的关系。

结果

我们观察到,与疾病不活动的SLE患者和健康对照相比,疾病活动的SLE患者外周B细胞中c-FLIP的百分比显著更高。狼疮外周B细胞中c-FLIP的表达与SLE疾病活动指数、红细胞沉降率、C反应蛋白、抗核小体抗体滴度、IL-4和IL-10呈正相关,与白细胞计数呈负相关。狼疮肾炎患者外周B细胞中c-FLIP的水平高于无狼疮肾炎的患者。

结论

我们的数据表明,c-FLIP的过表达与SLE的活动和严重程度相关。其过表达可能在防止SLE中B细胞凋亡方面发挥作用。c-FLIP过表达的原因可能是SLE患者中IL-4和IL-IO水平的升高。

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