中山大学附属第一医院风湿科,广东 广州 510080
李雪,博士生,研究方向:系统性红斑狼疮,E-mail:lixue56@mail2.sysu.edu.cn
收稿:2021-07-15,
纸质出版:2021-11-20
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李雪,曾琴,王双等.狼疮肾炎DN2细胞的CRAC和病情活动相关性分析[J].中山大学学报(医学科学版),2021,42(06):824-830.
LI Xue,ZENG Qin,WANG Shuang,et al.Expression of CRAC Protein Orai1 in DN2 Cells Is Correlated with Disease Activity in Lupus Nephritis[J].Journal of Sun Yat-sen University(Medical Sciences),2021,42(06):824-830.
李雪,曾琴,王双等.狼疮肾炎DN2细胞的CRAC和病情活动相关性分析[J].中山大学学报(医学科学版),2021,42(06):824-830. DOI: 10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2021.0604.
LI Xue,ZENG Qin,WANG Shuang,et al.Expression of CRAC Protein Orai1 in DN2 Cells Is Correlated with Disease Activity in Lupus Nephritis[J].Journal of Sun Yat-sen University(Medical Sciences),2021,42(06):824-830. DOI: 10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2021.0604.
目的
2
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
2
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
2
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
<0.000 1),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
=0.599 9,
P
=0.000 5)。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
<0.000 1),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
2
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
2
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
2
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
2
There was a statistically significant difference in the proportion of DN2 cells in peripheral blood among the four groups (
F
= 9.315,
P
<0.000 1). 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
=0.599 9,
P
=0.000 5). There was a statistically significant difference in the Orai1 expression in DN2 cells among the four groups (
F
= 7.935,
P
<0.000 1). 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
2
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.
Bengtsson AA , Ronnblom L . Systemic lupus erythematosus: still a challenge for physicians [J]. J Intern Med , 2017 , 281 ( 1 ): 52 - 64 .
Tsokos GC . Systemic lupus erythematosus [J]. N Engl J Med , 2011 , 365 ( 22 ): 2110 - 2121 .
Morales E , Galindo M , Trujillo H , et al . Update on lupus nephritis: looking for a new vision [J]. Nephron , 2021 , 145 ( 1 ): 1 - 13 .
杨念生 . 系统性红斑狼疮的治疗:问题及对策 [J]. 中华风湿病学杂志 , 2016 , 20 ( 11 ): 721 - 724 .
Yang NS . Problems and countermeasures in the treatment of systemic lupus erythematosus [J]. Chin J Rheumatol , 2016 , 20 ( 11 ): 721 - 724 .
Narváez J . Systemic lupus erythematosus [J]. Med Clin (Barc) , 2020 , 155 ( 11 ): 494 - 501 .
Wu C , Fu Q Guo Q , et al . Lupus-associated atypical memory B cells are mTORC1-hyperactivated and functionally dysregulated [J]. Ann Rheum Dis , 2019 , 78 ( 8 ): 1090 - 1100 .
何伟珍 , 张会昌 , 莫入 , 等 . 艾拉莫德联合昆仙胶囊治疗难治性狼疮性肾炎一例 [J]. 新医学 , 2020 , 51 ( 1 ): 71 - 73 .
He WZ , Zhang HC , Mo R , et al . Iguratimod combined with Kunxian capsule in treatment of refractory lupus nephritis: a case report [J]. J New Med , 2020 , 51 ( 1 ): 71 - 73 .
Minowa K , Amano H , Nakano S , et al . Elevated serum level of circulating syndecan-1 (CD138) in active systemic lupus erythematosus [J]. Autoimmunity , 2011 , 44 ( 5 ): 357 - 362 .
Abd-Elbaky NM , Albeltagy ES , Hammour AE , et al . Evaluation of serum β2-microglobulin in egyptian patients with systemic lupus erythematosus [J]. Egypt J Immunol , 2019 , 26 ( 2 ): 143 - 153 .
Feng Y , Yang M , Wu H , et al . The pathological role of B cells in systemic lupus erythematosus: From basic research to clinical [J]. Autoimmunity , 2020 , 53 ( 2 ): 56 - 64 .
Islam MS . Calcium signaling: from basic to bedside [J]. Adv Exp Med Biol , 2020 , 1131 : 1 - 6 .
Lunz V , Romanin C , Frischauf I , STIM 1 activation of orai1 [J]. Cell Calcium , 2019 , 77 : 29 - 38 .
Ma G , Wei M , He L , et al . Inside-out Ca2+ signalling prompted by STIM1 conformational switch [J]. Nat Commun , 2015 , 6 : 7826 .
Srikanth S , Jew M , Kim KD , et al . Junctate is a Ca2+-sensing structural component of Orai1 and stromal interaction molecule 1 (STIM1) [J]. Proc Natl Acad Sci U S A , 2012 , 109 ( 22 ): 8682 - 8687 .
YuF , Haas M , Glassock R , et al . Redefining lupus nephritis: clinical implications of pathophysiologic subtypes [J]. Nat Rev Nephrol , 2017 , 13 ( 8 ): 483 - 495 .
Jesus D , Matos A , Henriques C , et al . Derivation and validation of the SLE Disease Activity Score (SLE-DAS): a new SLE continuous measure with high sensitivity for changes in disease activity [J]. Ann Rheum Dis , 2019 , 78 ( 3 ): 365 - 371 .
Sachinidis A , Xanthopoulos K , Garyfallos A . Age-associated B Cells (ABCs) in the prognosis, diagnosis and therapy of systemic lupus erythematosus (SLE) [J]. Mediterr J Rheumatol , 2020 , 31 ( 3 ): 311 - 319 .
Jenks SA , Cashman KS , Zumaquero E , et al . Distinct Effector B cells induced by unregulated toll-like Receptor 7 contribute to pathogenic responses in systemic lupus erythematosus [J]. Immunity . ( 2018 ) 49 : 725 - 739 .
Baba Y , Kurosaki T . Role of calcium signaling in B cell activation and biology [J]. Curr Top Microbiol Immunol , 2015 , 393 : 143 - 174 .
Feske S , Picard C , Fischer A . Immunodeficiency due to mutations in ORAI1 and STIM1 [J]. Clin Immunol , 2010 , 135 ( 2 ): 169 - 182 .
Silva-Rojas R , Laporte J , Bhm J . STIM1/ORAI1 Loss-of-function and gain-of-function mutations inversely impact on SOCE and calcium homeostasis and cause multi-systemic mirror diseases [J]. Front Physiol , 2020 , 4, 11 : 604941 .
Mccarl CA , Picard C , Khalil S , et al . ORAI1 deficiency and lack of store-operated Ca2+ entry cause immunodeficiency, myopathy, and ectodermal dysplasia [J]. J Allergy Clin Immunol , 2009 , 124 ( 6 ): 1311 - 1318 .
Lacruz RS , Feske S . Diseases caused by mutations in ORAI1 and STIM1 [J]. Ann N Y Acad Sci , 2015 , 1356 ( 1 ): 45 - 79 .
Feske S , Gwack Y , Prakriya M , et al . A mutation in Orai1 causes immune deficiency by abrogating CRAC channel function [J]. Nature , 2006 , 441 ( 7090 ): 179 - 185 .
Liu S , Kiyoi T , Takemasa E , et al . Systemic lentivirus-mediated delivery of short hairpin RNA targeting calcium release-activated calcium channel 3 as gene therapy for collagen-induced arthritis [J]. J Immunol , 2015 , 194 ( 1 ): 76 - 83 .
Miyoshi M , Liu S , Morizane A , et al . Efficacy of constant long-term delivery of YM-58483 for the treatment of rheumatoid arthritis [J]. Eur J Pharmacol , 2018 , 824 : 89 - 98 .
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