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类风湿关节炎患者血浆Dickkopf-1的表达及其与外周血T细胞亚群的相关性

[Expression of plasma Dickkopf-1 in patients with rheumatoid arthritis and its correlation with peripheral blood T cell subsets].

作者信息

Cao D, Wang Y, Wang L Q, Sun X L, Huang F, Meng Y, Ren L L, Zhang X W

机构信息

Department of Rheumatology and Immunology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, China.

Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing 100044, China.

出版信息

Beijing Da Xue Xue Bao Yi Xue Ban. 2020 Sep 30;53(2):255-260. doi: 10.19723/j.issn.1671-167X.2021.02.004.

DOI:10.19723/j.issn.1671-167X.2021.02.004
PMID:33879894
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8072444/
Abstract

OBJECTIVE

To detect the levels of Dickkopf-1 (DKK-1) in the plasma of patients with rheumatoid arthritis (RA), and to analyze their correlation with peripheral blood T cell subsets and clinical indicators.

METHODS

Enzyme-linked immunosorbent assay (ELISA) was used to detect plasma DKK-1 levels in 32 RA patients and 20 healthy controls, and to record the various clinical manifestations and laboratory indicators of the RA patients, and flow cytometry to detect peripheral blood T cell subsets in the RA patients (Including Treg, nTreg, aTreg, sTreg, Teff, Tfh, CD4CD161T, CD8T, CD8CD161T cells). The plasma DKK-1 levels between the two groups were ompared, and its correlation with peripheral blood T cell subsets and clinical indicators analyzed.

RESULTS

(1) The plasma DKK-1 concentration of the RA patients was (124.97±64.98) ng/L. The plasma DKK-1 concentration of the healthy control group was (84.95±13.74) ng/L. The plasma DKK-1 level of the RA patients was significantly higher than that of the healthy control group ( < 0.05), and the percentage of CD8CD161T cells in the peripheral blood of the RA patients was significantly higher than that of the healthy control group ( < 0.05). (2) The plasma DKK-1 level was positively correlated with erythrocyte sedimentation rate (=0.406, =0.021), DAS28 score (=0.372, =0.036), immunoglobulin G(=0.362, =0.042), immunoglobulin A(=0.377, =0.033); it had no correlation with age, course of disease, C-reactive protein, rheumatoid factor, anti-cyclic citrullinated peptide antibody, immunoglobulin M, complement C3, complement C4, white blood cell, neutrophil ratio. (3) The plasma DKK-1 level in the RA patients was positively correlated with the percentage of peripheral blood CD161CD8T cells (=0.413, =0.019);it had no correlation with Treg, nTreg, aTreg, sTreg, Teff, Tfh, CD4CD161T, CD8T cells. (4) The percentage of CD161CD8T cells was negatively correlated with erythrocyte sedimentation rate (=-0.415, =0.004), C-reactive protein (=-0.393, =0.007), DAS28 score(=-0.392, =0.007), rheumatoid factor (=-0.535, < 0.001), anti-citrullinated protein antibody (=-0.589, < 0.001), immunoglobulin G(=-0.368, =0.012) immunoglobulin M (=-0.311, =0.035); it had no correlation with age, disease course, immunoglobulin A, complement C3, complement C4, white blood cell, and neutrophil ratio.

CONCLUSION

RA patients' plasma DKK-1 levels and the percentage of CD8CD161T cells in T cell subsets in peripheral blood increase, which may be related to the secretion of proinflammatory cytokines in patients; DKK-1 is involved in the regulation of bone homeostasis and can be used as a marker of bone destruction in RA.

摘要

目的

检测类风湿关节炎(RA)患者血浆中 Dickkopf-1(DKK-1)水平,并分析其与外周血 T 细胞亚群及临床指标的相关性。

方法

采用酶联免疫吸附测定(ELISA)法检测 32 例 RA 患者和 20 例健康对照者血浆 DKK-1 水平,记录 RA 患者的各种临床表现和实验室指标,采用流式细胞术检测 RA 患者外周血 T 细胞亚群(包括 Treg、nTreg、aTreg、sTreg、Teff、Tfh、CD4CD161T、CD8T、CD8CD161T 细胞)。比较两组血浆 DKK-1 水平,并分析其与外周血 T 细胞亚群及临床指标的相关性。

结果

(1)RA 患者血浆 DKK-1 浓度为(124.97±64.98)ng/L。健康对照组血浆 DKK-1 浓度为(84.95±13.74)ng/L。RA 患者血浆 DKK-1 水平显著高于健康对照组(P<0.05),RA 患者外周血 CD8CD161T 细胞百分比显著高于健康对照组(P<0.05)。(2)血浆 DKK-1 水平与红细胞沉降率(r=0.406,P=0.021)、DAS28 评分(r=0.372,P=0.036)、免疫球蛋白 G(r=0.362,P=0.042)、免疫球蛋白 A(r=0.377,P=0.033)呈正相关;与年龄、病程、C 反应蛋白、类风湿因子、抗环瓜氨酸肽抗体、免疫球蛋白 M、补体 C3、补体 C4、白细胞、中性粒细胞比例无关。(3)RA 患者血浆 DKK-1 水平与外周血 CD161CD8T 细胞百分比呈正相关(r=0.413,P=0.019);与 Treg、nTreg、aTreg、sTreg、Teff、Tfh、CD4CD161T、CD8T 细胞无关。(4)CD161CD8T 细胞百分比与红细胞沉降率(r=-0.415,P=0.004)、C 反应蛋白(r=-0.393,P=0.007)、DAS28 评分(r=-0.392,P=0.007)、类风湿因子(r=-0.535,P<0.001)、抗瓜氨酸化蛋白抗体(r=-0.589,P<0.001)、免疫球蛋白 G(r=-0.368,P=0.012)、免疫球蛋白 M(r=-0.311,P=0.035)呈负相关;与年龄、病程、免疫球蛋白 A、补体 C3、补体 C4、白细胞、中性粒细胞比例无关。

结论

RA 患者血浆 DKK-1 水平及外周血 T 细胞亚群中 CD8CD161T 细胞百分比升高,可能与患者促炎细胞因子分泌有关;DKK-1 参与骨稳态调节,可作为 RA 骨破坏的标志物。

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