骨髓基质细胞抗原2在原发性舍格伦综合征中的表达及意义

目的: 检测骨髓基质细胞抗原2(bone marrow stromal antigen-2,BST-2)在原发性舍格伦综合征（primary Sjögren's syndrome,pSS）患者唇腺及外周血淋巴细胞中的表达,探讨BST-2对淋巴细胞增殖的作用,以期为原发性舍格伦综合征的发病机制研究及药物治疗靶点的开发提供理论基础。方法: 应用实时定量PCR技术检测30例pSS患者及30例对照患者外周血单个核细胞（peripheral blood mononuclear cells,PBMCs）和唇腺组织中BST-2的表达水平,并与临床指标进行相关性分析。采用免疫组织化学对唇腺组织中的BST-2进行定位及半定量分析。通过分选外周血中的淋巴细胞,实时定量 PCR明确BST-2异常表达的淋巴细胞亚群,唇腺免疫组织化学连续切片染色验证。慢病毒转染人B淋巴细胞系以过表达BST-2,CCK8检测BST-2对细胞增殖活性的影响,流式细胞术分析其对细胞凋亡的影响。采用SPSS 16.0软件包对数据进行统计学分析。结果: 与对照患者相比,pSS患者唇腺组织中BST-2表达升高,阳性细胞主要是浸润腺体的B淋巴细胞。同时,pSS患者外周血CD19⁺ B细胞BST-2与对照组相比表达升高。过表达B细胞中的BST-2可以促进细胞增殖,抑制细胞凋亡。结论: BST-2在pSS患者外周血及唇腺组织中表达升高,BST-2主要定位于B淋巴细胞。推测BST-2通过促进B细胞在腺体中的增殖和浸润,从而参与pSS的发生与发展。

Expression of bone marrow stromal antigen-2 in primary Sjogren's syndrome and its clinical significance

PURPOSE: To analyze bone marrow stromal antigen-2 (BST-2) levels in labial glands, total peripheral blood mononuclear cells (PBMCs) and PBMC subpopulations from primary Sjögren's syndrome (pSS) patients, and explore the role of BST-2 in the pathogenesis of pSS. METHODS: PBMC subsets were positively separated using magnetic microbeads. BST-2 mRNA levels in labial glands, total PBMCs and PBMC subsets of 30 pSS and 30 healthy control (HC) subjects were investigated using real-time PCR (RT-PCR). Distribution of BST-2-positive cells in the labial glands was assessed by immunohistochemistry. Lentivirus transfection in Raji cells were conducted to determine the biologic function of BST-2. SPSS 16.0 software package was used for statistical analysis. Differences between the groups were analyzed using Mann Whitney test, and correlations were assessed using Spearman correlation analysis. RESULTS: BST-2 was increased in pSS labial glands and was positively correlated with VAS value for parotid gland swelling and rheumatoid factor and β2-microglobulin serum levels. BST-2 levels were significantly different between pSS patients with positive and negative expression of anti-SSA antibody. Positive focal infiltrating lymphocytes and adjacent ductal epithelial cells were observed in labial glands from pSS patients, while there were a few scattered positive ductal epithelial cells in controls. BST-2 was up-regulated in peripheral CD19⁺ B cells and labial CD19⁺ B cells from pSS patients. BST-2-overexpressed Raji cells possessed higher proliferative activity and lower apoptotic rate. CONCLUSIONS: BST-2 was aberrantly expressed in B cells of pSS patients, and expression in labial glands was positively correlated with important clinical characteristics. BST-2 might accelerate the progress of pSS by promoting infiltration of B cells.