[1]瞿 易,王茂源,唐有东,等.系统性红斑狼疮患者外周血CD4+T 细胞中ALKBH3-AS1 表达及其与Th17/Treg 和疾病活动度的相关性研究[J].现代检验医学杂志,2024,39(05):107-111+212.[doi:10.3969/j.issn.1671-7414.2024.05.020]
 QU Yi,WANG Maoyuan,TANG Youdong,et al.ALKBH3-AS1 Expression in Peripheral Blood CD4+T Cells of Patients with Systemic Lupus Erythematosus and Its Correlation with Th17/Treg and Disease Activity[J].Journal of Modern Laboratory Medicine,2024,39(05):107-111+212.[doi:10.3969/j.issn.1671-7414.2024.05.020]
点击复制

系统性红斑狼疮患者外周血CD4+T 细胞中ALKBH3-AS1 表达及其与Th17/Treg 和疾病活动度的相关性研究()
分享到:

《现代检验医学杂志》[ISSN:/CN:]

卷:
第39卷
期数:
2024年05期
页码:
107-111+212
栏目:
论著
出版日期:
2024-09-15

文章信息/Info

Title:
ALKBH3-AS1 Expression in Peripheral Blood CD4+T Cells of Patients with Systemic Lupus Erythematosus and Its Correlation with Th17/Treg and Disease Activity
文章编号:
1671-7414(2024)05-107-06
作者:
瞿 易1王茂源1唐有东2黄丽慧3
(1. 乐山市中医医院,四川乐山 614000;2. 峨眉山市中医医院,四川峨眉山 614200;3. 中南大学湘雅医院风湿免疫科,长沙 410011)
Author(s):
QU Yi1 WANG Maoyuan1 TANG Youdong2 HUNAG Lihui3
(1.Leshan Hospital of Traditional Chinese Medicine, Sichuan Leshan 614000, China;2. Hospital of Traditional Chinese Medicine of Emeishan City, Sichuan Emeishan 614200, China; 3.Department of Rheumatology and Immunology, Xiangya Hospital of Central South U
关键词:
系统性红斑狼疮长链非编码RNA辅助性T 细胞17/ 调节性T 细胞疾病活动度
分类号:
R593.241;R392.11
DOI:
10.3969/j.issn.1671-7414.2024.05.020
文献标志码:
A
摘要:
目的 研究分析系统性红斑狼疮(SLE)患者外周血CD4+T 细胞中ALKBH3-AS1 表达及其与辅助性T 细胞17/调节性T 细胞(Th17/Treg)和疾病活动度的相关性。方法 回顾性收集乐山市中医医院2020 年7 月~ 2024 年3 月确诊的系统性红斑狼疮患者60 例(SLE 组),根据SLE 疾病活动指数(SLEDAI)评分分为活动组(SLEDAI ≥ 10 分,n=33) 和稳定组(SLEDAI < 10 分,n=27);同时选取同期健康体检者52 例为对照组。收集三组一般资料,采集纳入者外周血离心得外周血单个核细胞(PBMC)。免疫磁珠法分离CD4+T 细胞,流式细胞仪检测Th17/Treg 占比情况,荧光定量PCR检测CD4+T 细胞中ALKBH3-AS1,维甲酸相关孤核受体(retinoidrelated orphan receptor γt,RORγt)相对表达量;酶联免疫吸附法(ELISA)测定血清转化生长因子(transforming growth factor,TGF)-β,白细胞介素-17(IL-17)含量;速率散射免疫比浊法测定补体C3,C4 水平变化。Pearson 分析ALKBH3-AS1,Th17 与SLE 患者各临床指标的相关性;Logistic 回归分析影响SLE 患者活动程度的因素。结果 对照组Hb,ALB, ALKBH3-AS1 mRNA,CD4+T,补体C3,补体C4 显著高于SLE 组(t/χ2/Z = 3.245,-11.169,-12.675,-17.829,-15.240,-19.212),RDW,TGF-β,RORγt,Th17/Treg,IL-17,CRP 显著低于SLE 组(t/χ2/Z=4.206,10.054,19.869,37.942,50.463,3.115),差异具有统计学意义(均P<0.05)。活动组ALB,ALKBH3-AS1 mRNA,CD4+T 显著低于稳定组(t/χ2/Z = -8.918,-2.483,-11.694),CRP,TGF-β,RORγt,Th17/Treg,IL-17 显著高于稳定组(t/χ2/Z = 3.121,5.671,1.787,14.720,12.044),差异具有统计学意义(均P <0.05)。Pearson 分析结果显示,ALKBH3-AS1 与CD4+T 呈正相关(r=0.663),与Th17/Treg,IL-17,TGF-β,RORγt,SLEDAI 指数呈负相关(r= -0.687,-0.715,-0.705,-0.678,-0.671);Th17/Treg 与CD4+T 呈负相关(r=-0.817),与IL-17,TGF-β,RORγt,SLEDAI 指数呈正相关(r=0.687,0.767,0.598,0.704)。Logistics 回归分析结果显示,CD4+T[OR(95%CI):0.715(0.304 ~ 0.904)] 占比增加、ALKBH3-AS1[OR(95%CI):0.654(0.320 ~ 0.987)] 表达上调为影响SLE 患者疾病活动度的保护因素,TGF-β[OR (95%CI):1.487(1.120 ~ 1.814)] 和IL-17[OR(95%CI):1.294(1.217 ~ 1.887)] 含量上调、Th17/Treg[OR(95%)CI:1.674(1.361 ~ 1.679)] 占比上调、RORγt[OR(95%)CI:1.547(1.252 ~ 1.941)] 相对表达量增加为影响SLE 患者疾病活动度的危险因素。结论 SLE 患者CD4+T 细胞中ALKBH3-AS1 表达下调,TGF-β,RORγt,IL-17 表达上调均与患者疾病活动度相关,可成为SLE 患者诊断、疾病活动及疗效评估的潜在生物标志物。
Abstract:
Objective To investigate the expression of ALKBH3-AS1 in peripheral blood CD4+T cells of patients with systemic lupus erythematosus(SLE)and its correlation with T helper cell 17/ regulatory T cells(Th17/Treg )and disease activity. Methods A total of 60 patients diagnosed with SLE in Leshan Hospital of Traditional Chinese Medicine from July 2020 to March 2024 were retrospectively collected. According to SLEDAI score, they were divided into active group (n=33, SLEDAI ≥ 10 score) and stable group (n=27,SLEDAI < 10 score). At the same time, 52 healthy subjects were selected as control group.The general data of three groups were collected and peripheral blood mononuclear cell(PBMC)was obtained by centrifugation in peripheral blood. CD4+T cells were isolated by immunomagnetic beads, and Th17/Treg ratio was detected by flow cytometry. The relative expression levels of ALKBH3-AS1 and retinoid-related orphan receptor γt (RORγt) in CD4+T cells were detected by fluorescence quantitative PCR. The contents of transforming growth factor(TGF)-βand interleukin (IL)-17 in serum were determined by enzyme-linked immunosorbent assay(ELISA).The levels of C3 and C4 were determined by rate scattering immunoturbidimetry. Pearson analyzed the correlation between ALKBH3-AS1, Th17 and various clinical indicators in SLE patients. Logistic regression analysis of the influencing factors in patients with severe SLE showed that the difference was statistically significant. Results Hb,ALB, ALKBH3-AS1 mRNA,CD4+T,complement C3 and C4 in the control group were significantly higher than those in SLE group (t/χ2/Z = 3.245,-11.169,-12.675,-17.829,-15.240,-19.212),RDW, TGF-β, RORγt, Th17/Treg, IL- 17, CRP was significantly lower than that in SLE group (t/χ2/Z =4.206,10.054,19.869,37.942,50.463,3.115),and the differences were statistically significant (all P <0.05).ALB,ALKBH3-AS1 mRNA, CD4+T in the active group were significantly lower than those in the stable group(t/χ2/Z = -8.918,-2.483,-11.694),CRP,TGF-β,RORγt,Th17/Treg,and IL-17 were significantly higher than those in the stable group(t/χ2/Z= 3.121,5.671,1.787,14.720,12.044),and the differences were statistically significant (all P <0.05).Pearson analysis showed that ALKBH3-AS1 was positively correlated with CD4+T(r=0.663), and negatively correlated with Th17/Treg,IL-17,TGF-β,RORγt,SLEDAIindex(r= -0.687,-0.715,-0.705,-0.678, -0.671),Th17/Treg was negatively correlated with CD4+T(r= - 0.817), and positively correlated with IL-17, TGF-β, RORγt, SLEDAI index with statistical significance(r=0.687,0.767,0.598,0.704).Logistics regression analysis, the results show: Increased CD4+T[OR(95%CI): 0.715(0.304 ~ 0.904)] proportion and up-regulated ALKBH3-AS1[OR(95%CI): 0.654(0.320 ~ 0.987)] expression were protective factors affecting disease activity in SLE patients. The contents of TGF-β[OR (95%CI): 1.487(1.120 ~ 1.814)] and IL-17[OR(95%CI): 1.294(1.217 ~ 1.887)] were up-regulated, the proportion of Th17/Treg[OR(95%)CI: 1.674(1.361 ~ 1.679)] was up-regulated, and the relative expression of RORγt[OR(95%)CI: 1.547(1.252 ~ 1.941)] was increased as risk factors affecting disease activity in SLE patients.Conclusion The down-regulated expression of ALKBH3-AS1 and upregulated expression of TGF-β, RORγt and IL-17 in CD4+T cells of SLE patients are all correlated with disease activity, and can be potential biomarkers for diagnosis, disease activity and efficacy evaluation in SLE patients.

参考文献/References:

[1] ZUCCHI D, ELEFANTE E, SCHILIR? D, et al. One year in review 2022: systemic lupus erythematosus[J]. Clinical and Experimental Rheumatology, 2022, 40(1): 4-14.
[2] BARBER M R W, DRENKARD C, FALASINNU T, et al. Global epidemiology of systemic lupus erythematosus[J]. Nature Reviews Rheumatology, 2021, 17(9): 515-532.
[3] TU Jianxin, ZHENG Nan, MAO Chentong, et al. UCBSCs exosomes regulate Th17/Treg balance in patients with systemic lupus erythematosus via miR-19b/ KLF13[J]. Cells, 2022, 11(24): 4123.
[4] WU Han, CHEN Shuxian, LI Aifen, et al. LncRNA expression profiles in systemic lupus erythematosus and rheumatoid arthritis: emerging biomarkers and therapeutic targets[J]. Frontiers in Immunology, 2021, 12: 792884.
[5] CHEN Yicheng, KUO Pinyu, CHOU Yuchi, et al. Upregulated expression of Pro-apoptotic long noncoding RNA lincRNA-p21 with enhanced cell apoptosis in lupus nephritis[J]. International Journal of Molecular Sciences, 2020, 22(1): 301.
[6] 应振华, 张园, 王小冬. 《2020 中国系统性红斑狼疮诊疗指南》解读[J]. 浙江医学, 2022, 44(1): 1-5. YING Zhenhua, ZHANG Yuan, WANG Xiaodong. Interpretation of the 2020 Chinese guidelines for diagnosis and treatment of systemic lupus erythematosus[J]. Zhejiang Medical Journal, 2022, 44(1): 1-5.
[7] 孔滔, 饶舜, 朱伟, 等. 系统性红斑狼疮患者外周血T 淋巴细胞Mg2+ 转运蛋白1 水平表达及临床价值研究[J]. 现代检验医学杂志, 2024, 39(3): 157-163. KONG Tao, RAO Shun, ZHU Wei, et al. Study on the expression level of Magnesiun transporter protein 1 in peripheral blood T lymphocytes of patients with systemic lupus erythematosus and its clinical value[J]. Journal of Laboratory Medicine, 2024, 39(3): 157-163.
[8] CARRI?N-BARBER? I, SALMAN-MONTE T C, V?LCHEZ-OYA F, et al. Neuropsychiatric involvement in systemic lupus erythematosus: a review[J]. Autoimmunity Reviews, 2021, 20(4): 102780.
[9] YU Haitao, NAGAFUCHI Y, FUJIO K. Clinical and immunological biomarkers for systemic lupus erythematosus[J]. Biomolecules, 2021, 11(7): 928.
[10] PETRI? M, RADI? M. Is Th17-targeted therapy effective in systemic lupus erythematosus?[J]. Current Issues in Molecular Biology, 2023, 45(5): 4331-4343.
[11] ZHANG Yali, XIE Liyi, LU Wanhong, et al. LncRNA MIAT enhances systemic lupus erythematosus by upregulating CFHR5 expression via miR- 222 degradation[J]. Central European Journal of Immunology, 2021, 46(1): 17-26.
[12] CHUN Wa n g , TIAN J i l a i , ZHANG Yi n g . Transplantation of mesenchymal stem cells ameliorates systemic lupus erythematosus and upregulates B10 cells through TGF-β1[J]. Stem Cell Research & Therapy, 2021, 12(1): 512.
[13] AYANO M, HORIUCHI T. Complement as a biomarker for systemic lupus erythematosus[J]. Biomolecules, 2023, 13(2): 367.
[14] CHEN Yan, TAO Tingjun, WANG Weiliang, et al. Dihydroartemisinin attenuated the symptoms of mice model of systemic lupus erythematosus by restoring the Treg/Th17 balance[J]. Clinical and Experimental Pharmacology and Physiology, 2021, 48(4): 626-633.
[15] ZHAO Xingyun, WANG Shifen, WANG Shengjun, et al. mTOR signaling: a pivotal player in Treg cell dysfunction in systemic lupus erythematosus[J]. Clinical Immunology, 2022, 245: 109153.
[16] NANDAKUMAR K S, N?NDEL K. Editorial: systemic lupus erythematosus - predisposition factors, pathogenesis, diagnosis, treatment and disease models[J]. Frontiers in Immunology, 2022, 13: 1118180.

相似文献/References:

[1]王 森,黄太宏,高 硕,等.系统性红斑狼疮患者乙型肝炎病毒感染的分析研究[J].现代检验医学杂志,2016,31(01):41.[doi:10.3969/j.issn.1671-7414.2016.01.011]
 WANG Sen,HUANG Tai-hong,GAO Shuo,et al.Prevalence of Hepatitis B Virus Infection in Systemic Lupus Erythematosus Patients[J].Journal of Modern Laboratory Medicine,2016,31(05):41.[doi:10.3969/j.issn.1671-7414.2016.01.011]
[2]宋宏岩a,王 红b,李 雷a,等.系统性红斑狼疮患者并发EB病毒或巨细胞病毒感染的回顾性分析[J].现代检验医学杂志,2016,31(01):144.[doi:10.3969/j.issn.1671-7414.2016.01.042]
 SONG Hong-yana,WANG Hongb,LI Leia,et al.Retrospective Analysis of Epstein Barr Virus or Cytomegalovirus Infection in Patients with Systemic Lupus Erythematosus[J].Journal of Modern Laboratory Medicine,2016,31(05):144.[doi:10.3969/j.issn.1671-7414.2016.01.042]
[3]张允奇a,陆学东b,张银辉b,等.SLE患者血清胱抑素C与血脂的相关性分析[J].现代检验医学杂志,2015,30(04):63.[doi:10.3969/j.issn.1671-7414.2015.04.017]
 ZHANG Yun-qia,LU Xue-dongb,ZHANG Yin-huib,et al.Correlation Analysis of Serum Cystatin C and Lipids Levels in Patients with Systemic Lupus Erythematosus[J].Journal of Modern Laboratory Medicine,2015,30(05):63.[doi:10.3969/j.issn.1671-7414.2015.04.017]
[4]朱琴芳,丁倩倩,俞钱,等.CD40-1C/T基因多态性与系统性红斑狼疮的相关性研究[J].现代检验医学杂志,2015,30(06):46.[doi:10.3969/j.issn.1671-7414.2015.06.013]
 ZHU Qin-fang,DING Qian-qian,YU Qian,et al.Association of CD40 Gene Polymorphism with the Systemic Lupus Erythematosus[J].Journal of Modern Laboratory Medicine,2015,30(05):46.[doi:10.3969/j.issn.1671-7414.2015.06.013]
[5]柏明见,冯璟,冯珍如,等.血清清蛋白测定在系统性红斑狼疮活动性评估中的应用价值[J].现代检验医学杂志,2015,30(06):116.[doi:10.3969/j.issn.1671-7414.2015.06.035]
 BAI Ming-jian,FENG Jing,FENG Zhen-ru,et al.Application Value of Serum Albumin for Disease Activity of Patient with Systemic Lupus Erythematosus[J].Journal of Modern Laboratory Medicine,2015,30(05):116.[doi:10.3969/j.issn.1671-7414.2015.06.035]
[6]张 振,李 芬.ceRNA与肿瘤[J].现代检验医学杂志,2016,31(04):128.[doi:10.3969/j.issn.1671-7414.2016.04.036]
[7]丁 海,高 硕,魏红霞,等.系统性红斑狼疮患者外周血SOCS-1基因甲基化的检测及意义[J].现代检验医学杂志,2017,32(01):34.[doi:10.3969/j.issn.1671-7414.2017.01.010]
 DING Hai,GAO Shuo,WEI Hong-xia,et al.Detection and the Significance of SOCS-1 Gene Methylation Status in Peripheral Blood of Systemic Lupus Erythematosus Patients[J].Journal of Modern Laboratory Medicine,2017,32(05):34.[doi:10.3969/j.issn.1671-7414.2017.01.010]
[8]杨依骏,杜建钢,朱琴芳,等.系统性红斑狼疮患者血清IL-10和IL-17水平检测的临床意义[J].现代检验医学杂志,2017,32(03):71.[doi:10.3969/j.issn.1671-7414.2017.03.019]
 YANG Yi-jun,DU Jian-gang,ZHU Qin-fang,et al.Clinical Significance of Serum IL-10 and IL-17 in Patients with Systemic Lupus Erythematosus[J].Journal of Modern Laboratory Medicine,2017,32(05):71.[doi:10.3969/j.issn.1671-7414.2017.03.019]
[9]胡 伟,王 森,黄太宏,等.双阴性调节性T细胞(DN Tregs在系统性红斑狼疮患者外周血中的变化及意义[J].现代检验医学杂志,2017,32(04):25.[doi:10.3969/j.issn.1671-7414.2017.04.007]
 HU Wei,WANG Sen,HUANG Tai-hong,et al.Change and Clinical Significance of Peripheral Blood DN Tregs in Patients with Systemic Lupus Erythematosus[J].Journal of Modern Laboratory Medicine,2017,32(05):25.[doi:10.3969/j.issn.1671-7414.2017.04.007]
[10]白盈盈,朱光旭,潘兴华.长链非编码RNA对结直肠癌潜在诊断价值的研究进展[J].现代检验医学杂志,2018,33(01):161.[doi:10.3969/j.issn.1671-7414.2018.01.001]

备注/Memo

备注/Memo:
作者简介:瞿易(1977-),男,本科,主管技师,研究方向:医学检验,E-mail:leshanquyi@163.com。
更新日期/Last Update: 2024-09-15