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[血清C-C趋化因子配体19水平升高与系统性红斑狼疮患者B细胞异常相关]

[Increased serum C-C chemokine ligand 19 levels correlated with B cell abnormalities in systemic lupus erythematosus].

作者信息

Liu H J, Shi L J, Hu F L, Yao H H, Li Z G, Jia Y

机构信息

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

Department of Rheumatology and Immunology, Peking University International Hospital, Beijing 102206, China.

出版信息

Beijing Da Xue Xue Bao Yi Xue Ban. 2017 Oct 18;49(5):829-834.

PMID:29045964
Abstract

OBJECTIVE

To detect the levels of serum C-C chemokine ligand 19 (CCL19) in patients with systemic lupus erythematosus (SLE) and to evaluate the correlation between CCL19 expression and clinical features and laboratory parameters, trying to reveal the possible role of CCL19 in the pathogenesis of systemic lupus erythematosus.

METHODS

The levels of serum CCL19 were measured by enzyme linked immunosorbent assay (ELISA) in 90 patients with SLE and 30 healthy controls. These SLE patients included 75 patients who received treatment with glucocorticoids and disease-modifying anti-rheumatic drug (DMARD) and 15 patients without therapy. The frequencies of peripheral blood B cells and the B cell subsets were assessed in the patients with SLE by flow cytometry. The correlation between the clinical data, laboratory parameters, B cell subset frequencies and serum CCL19 levels were analyzed. Indepen-dent samples t test, paired t test, Pearson and Spearman correlation were used for statistical analyses.

RESULTS

The levels of CCL19 were markedly higher in the SLE patients without therapy and the patients with therapy than in the health controls[(596.25±409.19) ng/L and (422.90±395.84) ng/L vs. (157.79±125.23) ng/L, all P<0.001]. Serum CCL19 levels in the SLE patients without therapy were higher than the SLE patients who accepted glucocorticoids and DMARD treatment (P<0.05). The levels of serum CCL19 were positively correlated with anti-double stranded deoxyribonucleic acid (dsDNA), anti-nucleosome antibody (AnuA), IgA, IgG and IgM (r=0.38, P=0.007; r=0.332, P=0.029; r=0.519, P=0.007; r=0.461, P=0.018, respectively). Serum CCL19 levels in the SLE patients with photosensitivity, arthritis and secondary Sjögren's syndrome were higher than the SLE patients without photosensitivity, arthritis and secondary Sjögren's syndrome, respectively [(562.25±399.12) ng/L, (565.6±435.24) ng/L and (694.9±531.02) ng/L vs. (394.7±281.42) ng/L, (385.90±325.33) ng/L and (424.8±305.46) ng/L, all P<0.05]. The levels of serum CCL19 were positively correlated with the percentage of CD27-B cells and CD27-IgD-double-negative memory B cells (r=0.519, P=0.007; r=0.461, P=0.018, respectively). However, the levels of serum CCL19 were negatively correlated with the percentage of CD27 memory B cells and CD27IgD switched memory B cells (r=-0.433, P=0.027; r=-0.616, P=0.001, respectively).

CONCLUSION

The increased serum CCL19 levels in SLE patients were associated with the production of autoantibodies, and CCL19 might be involved in the pathogenesis of SLE by disturbing the homeostasis of B cell subsets.

摘要

目的

检测系统性红斑狼疮(SLE)患者血清C-C趋化因子配体19(CCL19)水平,评估CCL19表达与临床特征及实验室参数之间的相关性,试图揭示CCL19在系统性红斑狼疮发病机制中的可能作用。

方法

采用酶联免疫吸附测定(ELISA)法检测90例SLE患者和30例健康对照者血清CCL19水平。这些SLE患者包括75例接受糖皮质激素和改善病情抗风湿药物(DMARD)治疗的患者以及15例未接受治疗的患者。采用流式细胞术评估SLE患者外周血B细胞及其亚群的频率。分析临床数据、实验室参数、B细胞亚群频率与血清CCL19水平之间的相关性。采用独立样本t检验、配对t检验、Pearson和Spearman相关性分析进行统计学分析。

结果

未接受治疗的SLE患者和接受治疗的SLE患者血清CCL19水平均显著高于健康对照者[(596.25±409.19)ng/L和(422.90±395.84)ng/L vs.(157.79±125.23)ng/L,P均<0.001]。未接受治疗的SLE患者血清CCL19水平高于接受糖皮质激素和DMARD治疗的SLE患者(P<0.05)。血清CCL19水平与抗双链脱氧核糖核酸(dsDNA)、抗核小体抗体(AnuA)、IgA、IgG和IgM呈正相关(r分别为0.38,P=0.007;r=0.332,P=0.029;r=0.519,P=0.007;r=0.461,P=0.018)。有光敏性、关节炎和继发性干燥综合征的SLE患者血清CCL19水平分别高于无光敏性、关节炎和继发性干燥综合征的SLE患者[(562.25±399.12)ng/L、(565.6±435.24)ng/L和(694.9±531.02)ng/L vs.(394.7±281.42)ng/L、(385.90±325.33)ng/L和(424.8±305.46)ng/L,P均<0.05]。血清CCL19水平与CD27-B细胞和CD27-IgD双阴性记忆B细胞百分比呈正相关(r分别为0.519,P=0.007;r=0.461,P=0.018)。然而,血清CCL19水平与CD27记忆B细胞和CD27IgD转换记忆B细胞百分比呈负相关(r分别为-0.433,P=0.027;r=-0.616,P=0.001)。

结论

SLE患者血清CCL19水平升高与自身抗体产生有关,CCL19可能通过扰乱B细胞亚群的稳态参与SLE的发病机制。