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外周血中布鲁顿酪氨酸激酶表达增加与狼疮肾炎有关。

Increased expression of Bruton's tyrosine kinase in peripheral blood is associated with lupus nephritis.

机构信息

Department of Rheumatology & Immunology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu, 210008, China.

出版信息

Clin Rheumatol. 2018 Jan;37(1):43-49. doi: 10.1007/s10067-017-3717-3. Epub 2017 Jun 14.

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease manifested by multiorgan impairment. It is reported that B cells participate in the onset of SLE. Bruton's tyrosine kinase (Btk), as a downstream signaling molecule of B cell antigen receptor (BCR) signaling pathway, is involved in the development, activation, and survival of B cells. The aim of our study was to explore the specific role of Btk in lupus nephritis (LN). We determined the percentages of Btk+ B cells in peripheral blood mononuclear cells (PBMCs) from SLE patients by flow cytometry and analyzed the correlation between the percentage of Btk+ B cells and lupus-related clinical indexes. Immunohistochemistry was used to detect the Btk expression in kidney from LN patients and tumor surrounding tissues. Compared with controls, the frequency of Btk+ B cells in SLE patients was upregulated (p < 0.01), and it was significantly correlated with the SLE Disease Activity Index (SLEDAI) (p < 0.01), levels of plasma anti-dsDNA antibody (p < 0.05), the amount of 24-h urine protein (p < 0.05), and levels of plasma C3 (p < 0.05). The frequency of Btk+ B cells in the patients with LN was significantly higher than those without LN (p < 0.05). Although the Btk expression in glomerulus of LN patients was significantly increased compared with controls (p < 0.001), but it had no correlation with the renal pathology activity index, SLEDAI, or 24-h urine protein. In conclusion, the increased expression of Btk in peripheral blood was correlated with LN, indicating that it may be a therapeutic target for SLE.

摘要

系统性红斑狼疮(SLE)是一种多器官损害为表现的自身免疫性疾病。有报道称 B 细胞参与了 SLE 的发病。布鲁顿酪氨酸激酶(Btk)作为 B 细胞抗原受体(BCR)信号通路的下游信号分子,参与 B 细胞的发育、激活和存活。本研究旨在探讨 Btk 在狼疮肾炎(LN)中的具体作用。我们通过流式细胞术测定了 SLE 患者外周血单个核细胞(PBMC)中 Btk+B 细胞的百分比,并分析了 Btk+B 细胞的百分比与狼疮相关临床指标之间的相关性。免疫组织化学检测了 LN 患者肾脏和肿瘤周围组织中 Btk 的表达。与对照组相比,SLE 患者 Btk+B 细胞的频率上调(p<0.01),且与 SLE 疾病活动指数(SLEDAI)显著相关(p<0.01),与血浆抗 dsDNA 抗体水平(p<0.05)、24 小时尿蛋白量(p<0.05)和血浆 C3 水平显著相关(p<0.05)。LN 患者的 Btk+B 细胞频率明显高于无 LN 患者(p<0.05)。尽管 LN 患者肾小球中 Btk 的表达明显高于对照组(p<0.001),但与肾病理活动指数、SLEDAI 或 24 小时尿蛋白均无相关性。总之,外周血中 Btk 的表达增加与 LN 相关,表明其可能是 SLE 的治疗靶点。

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