Conti Fabrizio, Spinelli Francesca Romana, Truglia Simona, Miranda Francesca, Alessandri Cristiano, Ceccarelli Fulvia, Bombardieri Michele, Giannakakis Konstantinos, Valesini Guido
Department of Internal Medicine and Medical Specialties-Rheumatology, Sapienza University of Rome, 00161 Rome, Italy.
Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Queen Mary University of London, London EC1M 6BQ, UK.
Mediators Inflamm. 2016;2016:7697592. doi: 10.1155/2016/7697592. Epub 2016 Aug 21.
Objective. The study aimed at locating and quantifying Toll Like Receptor (TLR) 3, 7, 8, and 9 expression in kidney of patients with lupus nephritis (LN) and correlating them with clinicopathological features. Methods. Kidney sections from 26 LN patients and 4 controls were analyzed by immunohistochemistry using anti-human TLR3, TLR7, TLR8, and TLR9 polyclonal antibodies; the number of TLR-positive nuclei/mm(2) was evaluated on digitalized images. Results. Compared to controls, LN showed a significantly higher amount of glomerular and tubulointerstitial TLR9 (p = 0.003 and p = 0.007), whole and tubulointerstitial TLR3 (p = 0.026 and p = 0.031), and a higher tubulointerstitial TLR7 (p = 0.022). TLR9 positively correlated with activity index (p = 0.0063) and tubular TLR7 with chronicity index (p = 0.026). TLR9 positively correlated with Renal-SLEDAI (p = 0.01). Conclusions. This is the first study quantifying kidney expressions of TLRs in LN patients; the results show an overexpression of TLR3, TLR7, and TLR9 and demonstrate a correlation with clinicopathological indices supporting a role of these mediators in the pathogenesis of LN.
目的。本研究旨在定位和定量狼疮性肾炎(LN)患者肾脏中Toll样受体(TLR)3、7、8和9的表达,并将其与临床病理特征相关联。方法。使用抗人TLR3、TLR7、TLR8和TLR9多克隆抗体,通过免疫组织化学分析26例LN患者和4例对照的肾脏切片;在数字化图像上评估TLR阳性细胞核的数量/平方毫米。结果。与对照组相比,LN患者肾小球和肾小管间质的TLR9表达量显著更高(p = 0.003和p = 0.007),全肾和肾小管间质的TLR3表达量更高(p = 0.026和p = 0.031),肾小管间质的TLR7表达量更高(p = 0.022)。TLR9与活动指数呈正相关(p = 0.0063),肾小管TLR7与慢性指数呈正相关(p = 0.026)。TLR9与肾脏SLEDAI呈正相关(p = 0.01)。结论。这是第一项定量LN患者肾脏中TLR表达的研究;结果显示TLR3、TLR7和TLR9表达上调,并证明与临床病理指标相关,支持这些介质在LN发病机制中的作用。