趋化因子配体19在系统性红斑狼疮中的表达及其与B细胞异常的相关性研究

目的 检测趋化因子配体19(C-C chemokine ligand 19, CCL19)在系统性红斑狼疮(systemic lupus erythematosus, SLE)患者血清中的表达,并分析其与SLE患者临床和实验室指标的关系,探讨CCL19在SLE发病机制中的可能作用。方法 采用酶联免疫吸附试验(enzyme linked immunosorbent assay, ELISA)法检测90例SLE患者(未接受过糖皮质激素和免疫抑制剂治疗的初治患者15例,曾治疗过的患者75例)和30名健康对照血清中CCL19的表达水平,分析SLE患者血清CCL19水平与临床特征和实验室指标的相关性。利用流式细胞术检测SLE患者B细胞及其亚群的比例,并进行血清CCL19水平与B细胞及其亚群比例的相关性分析。数据分析采用独立样本t检验、配对t检验、Pearson和Spearman相关分析。结果 (1)SLE初治患者和经治患者血清CCL19表达水平分别为(596.25±409.19) ng/L和(422.90±395.84) ng/L]显著高于健康对照组(157.79±125.23) ng/L,P均<0.001],初治患者组血清CCL19表达水平又高于经治患者组(P<0.05);(2)SLE患者血清CCL19表达水平与抗双链脱氧核糖核酸(double-stranded deoxyribonucleic acid, dsDNA)抗体、抗核小体抗体(anti-nucleosome antibody, AnuA)水平呈正相关(分别为r=0.38, P=0.007; r=0.332, P=0.029),与免疫球蛋白IgA、IgG、IgM水平呈正相关(分别为r=0.30, P=0.005; r=0.31, P=0.003; r=0.469, P=0.0001);(3)SLE有光过敏、关节炎和继发干燥综合征患者血清CCL19表达水平分别为(562.25±399.12) ng/L、(565.6±435.24) ng/L和(694.9±531.02) ng/L]分别较无光过敏、无关节炎和未继发干燥综合征SLE患者高分别为(394.7±281.42) ng/L、(385.90±325.33) ng/L和(424.8±305.46) ng/L],P均<0.05;(4)血清CCL19水平与外周血CD27^-B 细胞和CD27^-IgD^-双阴性记忆性 B 细胞的比例呈正相关(分别为r=0.519, P=0.007; r=0.461, P=0.018),与CD27⁺记忆性B细胞和CD27⁺IgD^-转化后记忆性B细胞的比例呈负相关(分别为r=-0.433, P=0.027; r=-0.616, P=0.001)。结论 SLE患者血清中高表达CCL19,与自身抗体的产生显著相关,CCL19可能通过影响B细胞亚群分布的内稳态参与SLE发病。

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

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.Independent 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 Sj(o)gren's syndrome were higher than the SLE patients without photosensitivity,arthritis and secondary Sj(o)gren'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 CD27 + IgD-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.