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, CD4+CD161+T, CD8+T, CD8+CD161+T 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 (P < 0.05), and the percentage of CD8+CD161+T cells in the peripheral blood of the RA patients was significantly higher than that of the healthy control group (P < 0.05). (2) The plasma DKK-1 level was positively correlated with erythrocyte sedimentation rate (r=0.406, P=0.021), DAS28 score (r=0.372, P=0.036), immunoglobulin G(r=0.362, P=0.042), immunoglobulin A(r=0.377, P=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 CD161+CD8+T cells (r=0.413, P=0.019);it had no correlation with Treg, nTreg, aTreg, sTreg, Teff, Tfh, CD4+CD161+T, CD8+T cells. (4) The percentage of CD161+CD8+T cells was negatively correlated with erythrocyte sedimentation rate (r=-0.415, P=0.004), C-reactive protein (r=-0.393, P=0.007), DAS28 score(r=-0.392, P=0.007), rheumatoid factor (r=-0.535, P < 0.001), anti-citrullinated protein antibody (r=-0.589, P < 0.001), immunoglobulin G(r=-0.368, P=0.012) immunoglobulin M (r=-0.311, P=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 CD8+CD161+T 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.
目的: 检测类风湿关节炎(rheumatoid arthritis，RA)患者血浆Dickkopf-1(DKK-1)水平，并分析其与外周血T细胞亚群、临床指标之间的相关性。
方法: 采用酶联免疫吸附法(enzyme linked immunosorbent assay，ELISA)检测32例RA患者及20例健康对照者的血浆DKK-1的水平，并记录RA患者的各项临床表现和实验室指标。流式细胞仪检测RA患者外周血T细胞亚群(包括Treg、nTreg、aTreg、sTreg、Teff、Tfh、CD4+CD161+T、CD8+T、CD8+CD161+T细胞)。比较两组血浆DKK-1的水平，并分析其与外周血T细胞亚群、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CD8+CD161+T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、白细胞计数、中性粒细胞百分比无相关性。(3)RA患者血浆DKK-1水平与外周血CD8+CD161+T细胞百分比呈正相关(r=0.413，P=0.019)；与Treg、nTreg、aTreg、sTreg、Teff、Tfh、CD4+CD161+T、CD8+T细胞无相关性。(4)外周血CD161+CD8+T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)、抗环瓜氨酸肽抗体(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、白细胞计数、中性粒细胞百分比无相关性。
结论: RA患者血浆DKK-1水平和外周血T细胞亚群中的CD8+CD161+T细胞百分比均升高，可能与患者体内促炎细胞因子的分泌有关；DKK-1参与骨稳态的调节，可用作RA骨破坏的标志物。
Keywords: Dickkopf-1; Rheumatoid arthritis; T cells.