狼疮性肾炎患者血清中CXCL9、CXCL10、CXCL11的表达研究
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摘要
目的观察狼疮性肾炎的临床病理特征,关注患者血清中CXC趋化因子配体9(CXCL9)、CXC趋化因子配体10(CXCL10)、CXC趋化因子配体11(CXCL11)的表达,分析其临床意义。方法选择83例狼疮性肾炎患者作为观察组,均行肾穿刺进行病理活检,并留取空腹静脉血,选择21例健康的成人血清作为对照组,抽取空腹静脉血,检测血清中CXCL9、CXCL10、CXCL11的表达。结果 83例患者均有肾穿病理资料,其中Ⅱ型共1例(1. 2%),Ⅲ型共19例(22. 9%),Ⅳ共35例(42. 2%),Ⅴ型共27例(32. 5%),Ⅵ型1例(1. 2%)。免疫荧光显示IgA、IgG、IgM、C3、C4、C1q和纤维蛋白均明显沉积。电镜检查见多少不等的电子致密物。观察组血清中CXCL9、CXCL10和CXCL11的表达明显高于对照组(P <0. 05),观察组中CXCL9、CXCL10和CXCL11的表达与病理分型和SLE活动期相关(P <0. 05)。观察组中CXCL9和CXCL11二者间的表达呈正相关(r=0. 44,P <0. 05)。结论狼疮性肾炎患者血清中三种蛋白的表达升高,CXCL9和CXCL11具有正相关性,共同促进病变的进展。
Objective To observe the clinical pathological features of lupus nephritis,and to analyze the expression and clinical sinificance of CXCL9,CXCL10 and CXCL11 in patients with lupus nephritis. Methods A total of 83 patients with lupus nephritis who underwent renal puncture pathological biopsy were enrolled as observation group,the other 21 healthy subjects were enrolled as control group. The serum levels of CXCL9,CXCL10 and CXCL11 were detected and compared between the two groups. Results The renal pathological data were analyzed in observation group,in which,there was 1 case( 1. 2%) of type Ⅱ,19 cases( 22. 9%) of type Ⅲ,35 cases( 42. 2%) of type Ⅳ,27 cases( 32. 5%) of type Ⅴ,1 case( 1. 2%) of Ⅵ. The immunofluorescence results showed that IgA,IgG,IgM,C3,C4,C1 q and fibrin were obviously sedimentated. The electron microscopy could observe varying electron-dense substances,Moreover the expression levels of CXCL9,CXCL10 and CXCL11 in observation group were significantly higher than those in control group( P < 0. 05). The expressons of CXCL9,CXCL10 and CXCL11 were closely correlated with pathologic classification and SLE activity stage in observation group( P < 0. 05),and the expression levels of CXCL9 were positively correlated to those of CXCL11 in observation group( r = 0. 44,P < 0. 05). Conclusion The expression levels of CXCL9,CXCL10 and CXCL11 are increased in serum of patients with lupus nephritis,and there is a positive correlation between CXCL9 and CXCL11,which can promote the progress of the disease.
Objective To observe the clinical pathological features of lupus nephritis,and to analyze the expression and clinical sinificance of CXCL9,CXCL10 and CXCL11 in patients with lupus nephritis. Methods A total of 83 patients with lupus nephritis who underwent renal puncture pathological biopsy were enrolled as observation group,the other 21 healthy subjects were enrolled as control group. The serum levels of CXCL9,CXCL10 and CXCL11 were detected and compared between the two groups. Results The renal pathological data were analyzed in observation group,in which,there was 1 case( 1. 2%) of type Ⅱ,19 cases( 22. 9%) of type Ⅲ,35 cases( 42. 2%) of type Ⅳ,27 cases( 32. 5%) of type Ⅴ,1 case( 1. 2%) of Ⅵ. The immunofluorescence results showed that IgA,IgG,IgM,C3,C4,C1 q and fibrin were obviously sedimentated. The electron microscopy could observe varying electron-dense substances,Moreover the expression levels of CXCL9,CXCL10 and CXCL11 in observation group were significantly higher than those in control group( P < 0. 05). The expressons of CXCL9,CXCL10 and CXCL11 were closely correlated with pathologic classification and SLE activity stage in observation group( P < 0. 05),and the expression levels of CXCL9 were positively correlated to those of CXCL11 in observation group( r = 0. 44,P < 0. 05). Conclusion The expression levels of CXCL9,CXCL10 and CXCL11 are increased in serum of patients with lupus nephritis,and there is a positive correlation between CXCL9 and CXCL11,which can promote the progress of the disease.
引文
1王倩,刘伟,卢葳,等.系统性红斑狼疮患者血清中趋化因子CXCL9,CXCL10及CXCL11的检测.中国皮肤性病学杂志,2015,25:125-128.
2 Welcher AA,Boedigheimer M,Kivitz AJ,et al.Blockade of interferon-γnormalizes interferon-regulated gene expression and serum CXCL10 levels in patients with systemic lupus erythematosus.Arthritis Rheumatol,2015,67:2713-2722.
3 Bronger H,Singer J,Windmüller C,et al.CXCL9 and CXCL10 predict survival and are regulated by cyclooxygenase inhibition in advanced serous ovarian cancer.Br J Cancer,2016,115:553-563.
4 Benredjem B,Girard M,Rhainds D,et al.Mutational Analysis of Atypical Chemokine Receptor 3(ACKR3/CXCR7)Interaction with Its Chemokine Ligands CXCL11 and CXCL12.J Biol Chem,2017,292:31-42.
5陈莎莎,唐政,刘正钊,等.快速进展性狼疮性肾炎临床病理特征及预后研究.中国实用内科学杂志,2015,35:146-150.
6李文宇,覃霞,张兰方,等.CCR6-CCL20趋化轴在系统性红斑狼疮中的作用.广西医科大学学报,2016,33:476-479.
7 Vanheule V,Janssens R,Boff D,et al.The Positively Charged COOH-terminal Glycosaminoglycan-binding CXCL9(74-103)Peptide Inhibits CXCL8-induced Neutrophil Extravasation and Monosodium Urate Crystalinduced Gout in Mice.J Biol Chem,2015,290:21292-21304.
8 Kato D,Kawanishi C,Kishida I,et al.CXCL9 and CXCL10 gene polymorphisms in patients with rheumatoid arthritis.Rheumatol Int,2015,35:1319-1323.
9 Berres ml,Asmacher S,Lehmann J,et al.CXCL9 is a prognostic marker in patients with liver cirrhosis receiving transjugular intrahepatic portosystemic shunt.J Hepatol,2015,62:332-339.
10李琳,钱晓萍,杜娟,等.趋化因子CXCL9和CXCL10介导的胃癌免疫细胞浸润的探讨.现代肿瘤医学,2015,23:2899-2904.
11润袁敏,绕绘,江华,等.系统性红斑狼疮患者血清中趋化因子CXCL家族的含量检测及临床意义.海南医学院学报,2015,21:1733-1736.
12 Jansen A,Schoffelen T,Textoris J,et al.CXCL9,a promising biomarker in the diagnosis of chronic Q fever.BMC Infect Dis,2017,17:556-557.
13 Hoh BP,Umishakina H,Zuraihan Z,et al.Common variants of chemokine receptor gene CXCR3 and its ligands CXCL10 and CXCL11associated with vascular permeability of dengue infection in peninsular Malaysia.Hum Immunol,2015,76:421-426.
14尚鹏程,许娇,裴晓方.慢乙肝和重乙肝患者趋化因子的表达差异及干扰素治疗后的变化.现代预防医学,2017,44:882-885.
15 Mittermayr M,Streif W,Haas T,et al.Signal transducer and activator of transcription(STAT)3 inhibition delays the onset of lupus nephritis in MRL/lpr,mice.Clin Immunol,2015,158:221-230.
2 Welcher AA,Boedigheimer M,Kivitz AJ,et al.Blockade of interferon-γnormalizes interferon-regulated gene expression and serum CXCL10 levels in patients with systemic lupus erythematosus.Arthritis Rheumatol,2015,67:2713-2722.
3 Bronger H,Singer J,Windmüller C,et al.CXCL9 and CXCL10 predict survival and are regulated by cyclooxygenase inhibition in advanced serous ovarian cancer.Br J Cancer,2016,115:553-563.
4 Benredjem B,Girard M,Rhainds D,et al.Mutational Analysis of Atypical Chemokine Receptor 3(ACKR3/CXCR7)Interaction with Its Chemokine Ligands CXCL11 and CXCL12.J Biol Chem,2017,292:31-42.
5陈莎莎,唐政,刘正钊,等.快速进展性狼疮性肾炎临床病理特征及预后研究.中国实用内科学杂志,2015,35:146-150.
6李文宇,覃霞,张兰方,等.CCR6-CCL20趋化轴在系统性红斑狼疮中的作用.广西医科大学学报,2016,33:476-479.
7 Vanheule V,Janssens R,Boff D,et al.The Positively Charged COOH-terminal Glycosaminoglycan-binding CXCL9(74-103)Peptide Inhibits CXCL8-induced Neutrophil Extravasation and Monosodium Urate Crystalinduced Gout in Mice.J Biol Chem,2015,290:21292-21304.
8 Kato D,Kawanishi C,Kishida I,et al.CXCL9 and CXCL10 gene polymorphisms in patients with rheumatoid arthritis.Rheumatol Int,2015,35:1319-1323.
9 Berres ml,Asmacher S,Lehmann J,et al.CXCL9 is a prognostic marker in patients with liver cirrhosis receiving transjugular intrahepatic portosystemic shunt.J Hepatol,2015,62:332-339.
10李琳,钱晓萍,杜娟,等.趋化因子CXCL9和CXCL10介导的胃癌免疫细胞浸润的探讨.现代肿瘤医学,2015,23:2899-2904.
11润袁敏,绕绘,江华,等.系统性红斑狼疮患者血清中趋化因子CXCL家族的含量检测及临床意义.海南医学院学报,2015,21:1733-1736.
12 Jansen A,Schoffelen T,Textoris J,et al.CXCL9,a promising biomarker in the diagnosis of chronic Q fever.BMC Infect Dis,2017,17:556-557.
13 Hoh BP,Umishakina H,Zuraihan Z,et al.Common variants of chemokine receptor gene CXCR3 and its ligands CXCL10 and CXCL11associated with vascular permeability of dengue infection in peninsular Malaysia.Hum Immunol,2015,76:421-426.
14尚鹏程,许娇,裴晓方.慢乙肝和重乙肝患者趋化因子的表达差异及干扰素治疗后的变化.现代预防医学,2017,44:882-885.
15 Mittermayr M,Streif W,Haas T,et al.Signal transducer and activator of transcription(STAT)3 inhibition delays the onset of lupus nephritis in MRL/lpr,mice.Clin Immunol,2015,158:221-230.