[1]刘素芳,赵　阳,贾　彬,等.类风湿关节炎患者血清DKK-1，CCL21水平与体液免疫指标的相关性研究[J].现代检验医学杂志,2022,37(03):33-36.[doi:10.3969/j.issn.1671-7414.2022.03.007]
　LIU Su-fang,ZHAO Yang,JIA Bin,et al.Study on the Correlation between Serum DKK-1, CCL21 and Humoral Immune Indexes in Patients with Rheumatoid Arthritis[J].Journal of Modern Laboratory Medicine,2022,37(03):33-36.[doi:10.3969/j.issn.1671-7414.2022.03.007]
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类风湿关节炎患者血清DKK-1，CCL21水平与体液免疫指标的相关性研究()
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《现代检验医学杂志》[ISSN:/CN:]

卷:
第37卷
期数:
2022年03期
页码:
33-36
栏目:
论　著
出版日期:
2022-05-15

文章信息/Info

Title:
Study on the Correlation between Serum DKK-1, CCL21 and Humoral Immune Indexes in Patients with Rheumatoid Arthritis
文章编号:
1671-7414（2022）03-033-05
作者:
刘素芳; 赵　阳; 贾　彬; 李俊芳
（邯郸市中心医院免疫科，河北邯郸 056001）
Author(s):
LIU Su-fang;  ZHAO Yang;  JIA Bin;  LI Jun-fang
(Department of Immunology ,the Central Hospital of Handan City , Hebei Handan 056001,China)
关键词:
类风湿关节炎; Dickkopf-1; 趋化因子; 体液免疫
分类号:
R593.22；R392.11
DOI:
10.3969/j.issn.1671-7414.2022.03.007
文献标志码:
A
摘要:
目的　探讨类风湿关节炎（ rheumatoid arthritis ，RA）患者血清 Dickkopf-1（DKK-1），趋化因子（ chemokine， CCL）21水平与体液免疫指标的相关性。方法　选择 2018年 3月～ 2020年 6月邯郸市中心医院免疫科收治的 120例 RA患者（ RA组）和 117例体检志愿者（对照组），根据 28个关节疾病活动度（ disease activity score 28，DAS28）评分将 RA组分为低度组（ 2.6～ 3.2分，38例）、中度组（ 3.3～ 5.1分，50例）和重度组（＞ 5.1分，32例）。检测血清 DKK-1，CCL21，免疫球蛋白 A（immunoglobulin A， IgA）、免疫球蛋白 G（IgG）、免疫球蛋白 M（IgM）、免疫球蛋白 E（IgE）、补体 C3和补体 C4水平。分析 DKK-1，CCL21与 IgG，IgA，IgM，IgE，补体 C3，补体 C4之间相关性。结果　RA组血清 DKK-1（72.14±15.26 pg/ml），CCL21（285.16±32.16 pg/ml），IgG（16.35±4.56 g/L），IgA（3.65±0.52 g/L）和 IgM（1.95±0.42 g/L）水平高于对照组（ 43.26±7.46 pg/ml，170.06±20.41pg/ml，10.35±1.65g/L，2.02±0.24g/ L，1.42±0.39g/L），差异均有统计学意义（ t=10.061～ 32.803，均 P＜ 0.05），补体 C3（1.05±0.16 g/L）和补体 C4（0.15±0.07 g/L）水平低于对照组（ 1.39±0.25g/L，0.36±0.11g/L），差异均有统计学意义（ t=12.502，17.579，均 P＜ 0.05）。重度组血清 DKK-19（83.26±3.09 pg/ml），CCL21（310.06±6.45 pg/ml），IgG(19.84±0.68 g/L），IgA（4.14±0.03 g/ L）和 IgM（2.28±0.06 g/L）水平高于中度组（ 74.90±6.59 pg/ml，289.75±12.54 pg/ml，17.40±2.11 g/L,3.71±0.26 g/ L,2.03±0.16 g/L）和轻度组（59.15±2.34 pg/ml, 258.15±4.06 pg/ml, 12.03±0.21 g/L, 3.16±0.02 g/L, 1.57±0.03 g/L），差异均有统计学意义（ t=6.322～ 162.999, 均 P＜ 0.05）；补体 C3和补体 C4水平低于中度组 (1.18±0.02 g/L vs 1.07±0.05 g/L，0.20±0.01 g/L vs 0.16±0.04 g/L)和轻度组 (0.91±0.02 g/L，0.09±0.01 g/L), 差异均有统计学意义（t= 5.536～ 45.847，均 P＜ 0.05）。中度组血清 DKK-1，CCL21，IgG，IgA和 IgM水平高于轻度组（ t=12.993～ 17.468，均 P＜ 0.05）；补体 C3和补体 C4水平低于轻度组（ t=18.607，10.527，均 P＜ 0.05）,差异均有统计学意义。 RA患者血清 DKK-1和 CCL21水平与 IgG，IgA和 IgM呈正相关（ r=0.742～ 0.805，均 P＜ 0.05），与补体 C3和补体 C4水平呈负相关（ r= -0.736～ -0.744，均 P＜ 0.05），各组之间的 IgE差异均无统计学意义 (F=0.869，P＞ 0.05)，DKK-1和 CCL21与 IgE也无相关性 (r=0.168，0.203，均 P＞ 0.05)。结论　RA患者血清 DKK-1和 CCL21水平升高与 RA疾病活动程度以及 IgG，IgA和 IgM增高与补体 C3和 C4消耗有关。
Abstract:
Objective　To investigate the correlation between serum Dickkopf-1 (DKK-1), chemokine (CCL21) and humoral immune indexes in patients with rheumatoid arthritis (RA). Methods　A total of 120 RA patients (RA group) and 117 physical examination volunteers (control group) admitted to Department of Immunology,the Central Hospital of Handan City from March 2018 to June 2020 were selected. According to DAS28 scores, the RA group was divided into low-grade group (2.6~3.2 points, 38 cases) and moderate group (3.3 ～ 5.1 points, 50 cases) and severe group ( ＞ 5.1 points, 32 cases).Serum levels of DKK-1, CCL21, immunoglobulin A (IgA), immunoglobulin G (IgG), immunoglobulin M (IgM), immunoglobulin E (IgE), complement C3 and complement C4 were detected.The correlation between DKK-1, CCL21 and IgG, IgA, IgM, IgE, complement C3 and complement C4 was analyzed. Results　The serum levels of DKK-1(72.14±15.26 pg/ml)，CCL21(285.16±32.16 pg/ml)， IgG(16.35±4.56 g/L)，IgA(3.65±0.52 g/L) and IgM(1.95±0.42 g/L ) in RA group were higher than those in control group（43.26±7.46 pg/ml, 170.06±20.41pg/ml, 10.35±1.65g/L, 2.02±0.24g/L，1.42±0.39g/L）, the differences were statistically significant (t=10.061~32.803, all P ＜ 0.05), and the levels of complement C3(1.05±0.16 g/L) and complement C4(0.15±0.07 g/L) were lower than those in control group （1.39±0.25g/L，0.36±0.11g/L）, the differences were statistically significant (t=12.502，17.579，all P ＜ 0.05).The serum levels of DKK-19（83.26±3.09 pg/ml）, CCL21（310.06±6.45 pg/ ml）, IgG(19.84±0.68 g/L）, IgA（4.14±0.03 g/L）and IgM（2.28±0.06 g/L） in severe group were higher than those in moderate group（74.90±6.59 pg/ml，289.75±12.54 pg/ml，17.40±2.11 g/L, 3.71±0.26 g/L, 2.03±0.16 g/L） and mild group（59.15±2.34 pg/ml, 258.15±4.06 pg/ml, 12.03±0.21 g/L,3.16±0.02 g/L,1.57±0.03 g/L）, the differences were statistically significant（t=6.322 ～ 162.999, all P ＜ 0.05）, and the levels of complement C3 and complement C4 in severe group were lower than those in moderate group(1.18±0.02 g/L vs 1.07±0.05 g/L，0.20±0.01 g/L vs 0.16±0.04 g/L) and mild group(0.91±0.02 g/L，0.09±0.01 g/L) ，the differences were statistically significant（t= 5.536 ～ 45.847, all P ＜ 0.05）. The serum levels of DKK-1, CCL21, IgG, IgA and IgM in moderate group were higher than those in mild group (t=12.993 ～ 17.468, all P ＜ 0.05), and the levels of complement C3 and complement C4 were lower than those in mild group (t=18.607, 10.527, all P ＜ 0.05) ，the differences were statistically significant，respectively.Serum DKK-1 and CCL21 levels in RA patients were positively correlated with IgG, IgA and IgM (r=0.742 ～ 0.805, all P ＜ 0.05), and negatively correlated with complement C3 and complement C4 levels (r=-0.736 ～ -0.744, all P ＜ 0.05). There was no significant difference in IgE between groups (F=0.869, P ＞ 0.05), DKK-1 and CCL21 were not correlated with IgE (r =0.168, 0.203 , all P ＞ 0.05).Conclusion　Serum DKK-1 and CCL21 levels were increased in RA patients, and the increase of DKK-1 and CCL21 levels were related to the activity of RA disease, the increase of IgG, IgA, IgM, and the depletion of complement C3 and C4.

参考文献/References:

[1] VAN DER WOUDE D, VAN DER HELM-VAN MIL A H M. Update on the epidemiology, risk factors, and disease outcomes of rheumatoid arthritis[J]. Best Pract Res Clin Rheumatol, 2018, 32(2): 174-187.
[2] 张微, 张润清, 于磊. 类风湿关节炎并发贫血女性患 者血清铁蛋白检测的临床价值[J]. 现代检验医学杂 志,2018,33(2):118-120,124. ZHANG Wei,ZHANG Runqing,YU Lei. Clinical value of serum ferritin detection in patients with rheumatoid arthritis complicated with anemia[J]. Journal of Modern Laboratory Medicine,2018,33(2):118-120,124.
[3] 詹泰河. 真实世界中血清TNF-α 与IL-6 在类风湿 关节炎中的作用[D]. 广州：南方医科大学, 2019． ZHAN Taihe. The role of serum TNF-α and IL-6 in rheumatoid arthritis in the real world [D]. Guangzhou: Southern Medical University, 2019
[4] REINHOLD S, BLANKESTEIJN W M. Wnt/ β-Catenin inhibitor dickkopf 1[J]. Arteriosclerosis Thrombosis and Vascular Biology, 2019, 39(2): 121- 123.
[5] KLAVDIANOU K, LIOSSIS S N, SAKKAS L, et al. The role of Dickkopf-1 in joint remodeling and fibrosis: A link connecting spondyloarthropathies and scleroderma[J]. Seminars in Arthritis and Rheumatism, 2017, 46(4): 430-438.
[6] 程瑞娟, 吴春玲, 肖卫国. 类风湿关节炎血清中 CCL19 和CCL21 的表达水平与肺间质病变的关系 [J]. 中国免疫学杂志,2018,34(1):91-94. CHENG Ruijuan ,WU Chunling ,XIAO Weiguo. Relationships between serum expression levels of CCL21 and CCL19 in rheumatoid arthritis and interstitial lung disease [J]. Chinese Journal of Immunology, 2018,34(1):91-94.
[7] 邱贵兴. 类风湿关节炎的诊断与治疗骨科专家共识 [J]. 中华骨科杂志,2012,32(12):1184-1186. QIU Guixing.Rheumatoid arthritis diagnosis and treatment of orthopedic experts consensus[J]. Chinese Journal of Orthopaedics,2012,32(12):1184-1186.
[8] 郭慧娟, 田冰超, 唐今扬, 等. 类风湿性关节炎、系 统性红斑狼疮及原发性干燥综合征肾损伤与体液 免疫的相关性研究[J]. 中国医药导报, 2020, 17(29): 115-118． GUO Huijuan,TIAN Bingchao,TANG Jinyang, et al. Correlation study between renal injury and humoral immunity in patients with rheumatoid arthritis,systemic lupus erythematosus and primary Sjogren’s syndrome[ J]. China Medical Herald,2020,17(29):115-118.
[9] VITA A A, ALJOBAILY H, LYONS D O, et al. Berberine delays onset of collagen-induced arthritis through T cell suppression [J]. International Journal of Molecular Sciences, 2021, 22(7): 3522.
[10] 王育.B 淋巴细胞与免疫五项在新生儿缺氧缺血 性脑病中的检测意义[J]. 中国妇幼保健, 2017, 32(22):5601-5605. WANG Yu.The significance of B lymphocyte and immune detection in neonatal hypoxic-ischemic encephalopathy[J]. Maternal and Child Health Care of China,2017,32(22):5601-5605.
[11] DAOUSSIS D, PAPACHRISTOU D J, DIMITROULAS T, et al. Dickkopf-1 is downregulated early and universally in the skin of patients with systemic sclerosis despite normal circulating levels[J]. Clinical and Experimental Rheumatology, 2018, 36 Suppl 113(4): 45-49.
[12] LI Jieping, GONG Wenlin, LI Xiaoxue, et al. Recent progress of Wnt pathway inhibitor dickkopf-1 in liver cancer[J]. Journal of Nanoscience and Nanotechnology, 2018, 18(8): 5192-5206.
[13] 李燕, 熊志伟．Dickkopf-1, LINGO-1, Caveolin-1 在 脑出血中的表达水平变化及其与病情严重程度的关 系[J]. 卒中与神经疾病, 2020, 27(3): 332-335, 340. LI Yan, XIONG Zhiwei. Expression level changes of Dickkopf-1, Lingo-1 and Caveolin-1 in cerebral hemorrhage and its correlation with the disease severity [J]. Stroke and Nervous Diseases, 2020, 27 (3): 332- 335, 340.
[14] RUARO B, CASABELLA A, PAOLINO S, et al. Dickkopf-1 (DKK-1) serum levels in systemic sclerosis and rheumatoid arthritis patients: correlation with the Trabecular Bone Score (TBS)[J]. Clinical Rheumatology, 2018, 37(11): 3057-3062.
[15] 李鹏花.DKK-1 在活动期类风湿关节炎中的相关性 研究[J]. 山西医药杂志,2019,48(2):232-234. LI Penghua.Correlation study of DKK-1 in active rheumatoid arthritis[J].Shanxi Medical Journal,2019,48(2):232-234.
[16] CHAE W J, EHRLICH A K, CHAN P Y, et al. The Wnt antagonist dickkopf-1 promotes pathological type 2 Cell-Mediated inflammation[J]. Immunity, 2016, 44(2): 246-258.
[17] CHAE W J, PARK J H, HENEGARIU O, et al. Membrane-bound Dickkopf-1 in Foxp3(+) regulatory T cells suppresses T-cell-mediated autoimmune colitis[J]. Immunology, 2017, 152(2): 265-275.
[18] 程瑞娟, 吴春玲, 肖卫国. 趋化因子CCL21 与类风 湿关节炎研究进展[J]. 中华风湿病学杂志, 2017, 21(9): 641-644. CHENG Ruijuan,WU Chunling,XIAO Weiguo. Research progress of chemokine CCL21 and rheumatoid arthritis[J].Chinese Journal of Rheumatology, 2017,21(9):641-644.
[19] 吴娟, 段晓玲, 谢璠, 等. 趋化因子CCL21 在类风湿 关节炎发病中作用的研究进展[J]. 山东医药, 2020, 60 (31): 105-108. WU Juan, DUAN Xiaoling, XIE Fan, et al. Research progress on the role of chemokine CCL21 in the pathogenesis of rheumatoid arthritis [J]. Shandong Medical Journal, 2020,60 (31): 105-108.
[20] CHEN Yang, SHAO Zhe, JIANG Erhui, et al. CCL21/ CCR7 interaction promotes EMT and enhances the stemness of OSCC via a JAK2/STAT3 signaling pathway[J].Journal of Cellular Physiology, 2020, 235(9): 5995-6009.
[21] JOUTOKU Z, ONODERA T, MATSUOKA M, et al. CCL21/CCR7 axis regulating juvenile cartilage repair can enhance cartilage healing in adults[J]. Scientific Reports, 2019, 9(1): 5165.
[22] MCHUGH J. CCL21-CCR7 axis in RA: linking inflammation and bone erosion[J]. Nature Reviews Rheumatology, 2019, 15(10): 576.
[23] VAN RAEMDONCK K, UMAR S, SHAHRARA S. The pathogenic importance of CCL21 and CCR7 in rheumatoid arthritis [J]. Cytokine Growth Factor Rev, 2020, 55:86-93.
[24] VAN RAEMDONCK K, UMAR S, PALASIEWICZ K, et al. CCL21/CCR7 signaling in macrophages promotes joint inflammation and Th17-mediated osteoclast formation in rheumatoid arthritis[J]. Cellular and Molecular Life Sciences , 2020, 77(7): 1387-1399.
[25] ZHAO Ruozhu, CHEN Xin, MA Weiwei, et al. A GPR174-CCL21 module imparts sexual dimorphism to humoral immunity[J]. Nature, 2020, 577(7790): 416- 420.

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备注/Memo

备注/Memo:
基金项目：河北省医学科学研究课题（20200477）；河北省卫生健康委员会资助。
作者简介：刘素芳（1982-），女，硕士研究生，主治医师，研究方向：风湿免疫，E-mail:xf692602@21cn.com。
通讯作者：李俊芳（1967-），女，硕士研究生，主任医师，研究方向：风湿免疫。
更新日期/Last Update: 1900-01-01