Toll样受体9在狼疮肾炎患者外周血B淋巴细胞和肾组织中的表达及临床意义

The expression and clinical significance of Toll-like receptor 9 on blood B cells and renal tissue in patients with lupus nephritis

目的探讨Toll样受体9（TLR9）在狼疮肾炎（LN）患者外周血B淋巴细胞和肾组织的表达及其临床意义。方法分别采用细胞内流式细胞术和免疫组织化学方法对埘照组和LN患者外周血B淋巴细胞及肾组织中TLR9表达情况进行比较，并对TLR9表达与临床指标相关性进行分析。结果活动期LN患者外周血CD19^＋B淋巴细胞TLR9的表达率高于非活动期LN患者及对照组（P〈0．01），且其表达率与SLE疾病活动指数（SLEDAI）评分、抗双链DNA（dsDNA）抗体滴度呈正相关（P〈0．01）。LN患者肾组织中肾小球、肾小管间质TLR9表达均较健康组织增高（P〈0．01），其中国际肾脏病学会／肾脏病理学会（ISN／RPS）的Ⅳ型LN肾组织TLR9表达水平较Ⅱ、Ⅲ、Ⅴ型升高（P〈0．01）．且肾小球TLR9表达水平与肾小球细胞增殖程度、肾脏病理活动指数、尿蛋白定量（24h）呈正相关（P〈O．01），与估计的肾小球滤过率（eGFR）呈负相关（P〈0．01）；肾小管间质TLR9表达水平与肾脏病理活动指数、肾小管间质损害程度、尿蛋白定量（24h）也呈正相关（P〈0．01），与eGFR呈负相关（P〈0．01）。结论TLR9参与了LN患者B淋巴细胞的异常活化及肾脏病理损伤过程。

Objective To investigate the role of Toll-like receptor 9 （TLR9） in patients with lupus nephritis （LN） and its clinical signifieance. Methods The expressions of TLR9 were examined on the renal tissue and peripheral blood CD19^＋ B lymphocytes of LN patients and healthy controls by immunohistochemistry and flow cytometry respectively. In addition, the renal histological index and clinical parameters were analyzed to elucidate the relationship between the expression of TLR9 and disease status. Results lntracellular TLR9 expression levels of B lymphocytes were elevated in patients with LN compared to healthy subjects, especially in those whose disease activity were scored greater than 10 by SLEDAI. The positive correlation was also observed between TLR9 expression levels and clinical measure of the SLEDAI and Anti-dsDNA （P〈0.01）. In kidneys of LN patients, TLR9 was expressed in glomerular and interstitial, but not in those of healthy controls （P〈0.01）. The expression of TLR9 was more prominent in the kidneys with severe proliferative histopathology lesions. Compared with the ISN/RPS revised pathologic class Ⅱ, class Ⅲ and class Ⅴ, the highest expression of TLR9 was observed in class Ⅳ （P〈0.01）. Moreover, the expression of TLR9 showed a strong tcorrelation with the renal histological index （P〈0.01）, the estimated glomerular fihration rate （P〈0.01） and 24-h urinary protein （P〈0.01）. Conclusion Up-regulated expression of TLR9 may he involved in the pathogenesis of B cell abnormal hyperactivity and the aggravated renal lesions in patients with LN.