狼疮肾炎DN2细胞的CRAC和病情活动相关性分析  

Expression of CRAC Protein Orai1 in DN2 Cells Is Correlated with Disease Activity in Lupus Nephritis

作　　者：李雪[1] 曾琴 王双 叶宝奎 杨念生[1] LI Xue;ZENG Qin;WANG Shuang;YE Bao-kui;YANG Nian-sheng(Department of Rheumatology,The First Affiliated Hospital,Sun Yat-sen University,Guangzhou 510080,China)

机构地区：[1]中山大学附属第一医院风湿科,广东广州510080

出　　处：《中山大学学报（医学科学版）》2021年第6期824-830,共7页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：国家自然科学基金(81971519)。

摘　　要：【目的】探讨狼疮肾炎(LN)患者外周血双阴性B细胞2(DN2)细胞的比例,以及DN2细胞钙离子释放激活的钙离子通道(CRAC)蛋白表达情况及其与临床相关性。【方法】流式细胞学检测健康对照者(HC,n=15)、狼疮肾炎(LN,n=30)、类风湿关节炎(RA,n=15)和原发性干燥综合征(pSS,n=15)患者外周血DN2细胞的比例以及DN2细胞CRAC蛋白Orai1表达情况;用单因素方差分析四组间差异,用Pearson相关性分析探讨Orai1表达与LN疾病活动指标的相关性。【结果】四组研究对象外周血DN2细胞比例差异有统计学意义(F=9.315,P<0.0001),LN患者DN2细胞比例显著高于HC、RA患者和pSS患者[(2.60±2.20)%vs.(0.68±0.56)%vs.(0.69±0.45)%vs.(1.04±0.72)%],并与24 h尿蛋白定量呈正相关(r=0.5999,P=0.0005)。四组研究对象DN2细胞的Orai1表达差异有统计学意义(F=7.935,P<0.0001),LN患者DN2细胞的Orai1表达显著高于HC、RA患者和pSS患者(2.30±1.50 vs.0.86±0.39 vs.1.34±0.57 vs.1.13±0.64),并与SLEDAI评分(r=0.56,P<0.005)、血抗dsDNA抗体水平(r=0.43,P<0.05)和24 h尿蛋白定量(r=0.44,P<0.05)水平呈正相关,与血补体C3水平(r=-0.39,P<0.05)呈负相关。【结论】LN患者DN2细胞比例增加,其Orai1表达增加,且与疾病活动度相关;DN2细胞的SOCE可能是LN潜在的治疗靶点。【Objective】The aim of this study is to investigate the proportion of DN2 cell and the correlation between the expression of calcium ion release activated calcium ion channel(Ca^(2+) release-activated Ca^(2+),CRAC)protein in DN2 cells and the clinical activity of lupus nephritis(LN).【Methods】Flow cytometry was used to detect the proportion of DN2 cells in healthy controls(HC,n=15),LN(HC,n=30),rheumatoid arthritis(RA,n=15)and primary Sjogren syndrome(pSS,n=15)patients and the expression of SOCE protein Orai1 in DN2 cells.One-way ANOVA was used to analyze the differences among the four groups.The correlation between Orai1 expression and LN disease activity was analyzed by Pearson correlation analysis.【Results】There was a statistically significant difference in the proportion of DN2 cells in peripheral blood among the four groups(F=9.315,P<0.0001).The proportion of DN2 cells in the peripheral blood of patients with LN was significantly higher than that of HC,RA and pSS[(2.60±2.20)%vs.(0.68±0.56)%vs.(0.69±0.45)%vs.(1.04±0.72)%]and was correlated with 24-hour urinary protein excretion(r=0.5999,P=0.0005).There was a statistically significant difference in the Orai1 expression in DN2 cells among the four groups(F=7.935,P<0.0001).The Orai1 expression in DN2 cells of LN was significantly higher than that of HC,RA and pSS(2.30±1.50 vs.0.86±0.39 vs.1.34±0.57 vs.1.13±0.64).Orai1 expression in DN2 cells was positively correlated with SLEDAI(r=0.56,P<0.005),blood anti-dsDNA antibody level(r=0.43,P<0.05)and 24-hour urinary protein excretion(r=0.44,P<0.05),and negatively correlated with complement C3(r=-0.39,P<0.05).【Conclusions】The proportion of DN2 cells and the expression of Orai1 increases in patients with LN and is correlated with disease activity.SOCE of DN2 cells may be a potential therapeutic target for LN.

关 键 词：狼疮肾炎 DN2细胞 钙离子释放激活的钙离子通道 Orai1 

分 类 号：R593.24[医药卫生—内科学]