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
发布时间：2019-01-02 12:33
【摘要】：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(P0.05);(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,ds DNA)抗体、抗核小体抗体(anti-nucleosome antibody,Anu A)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Ig A、Ig G、Ig M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-Ig D-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+Ig D-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。
[Abstract]:Objective: to detect the expression of chemokine ligand 19 (C-C chemokine ligand 19 CCL19) in the serum of patients with systemic lupus erythematosus (systemic lupus erythematosus,SLE), and to analyze the relationship between the expression of C-C chemokine ligand 19 and the clinical and laboratory parameters of SLE. To explore the possible role of CCL19 in the pathogenesis of SLE. Methods: enzyme linked immunosorbent assay (enzyme linked immunosorbent assay,ELISA) was used to detect 90 patients with SLE (15 patients without glucocorticoid and immunosuppressant therapy). The expression of CCL19 in serum of 75 patients who had been treated and 30 healthy controls were analyzed. The correlation between serum CCL19 level and clinical features and laboratory indexes in patients with SLE was analyzed. Flow cytometry was used to detect the proportion of B cells and their subsets in patients with SLE, and the correlation between serum CCL19 levels and B cells and their subsets was analyzed. The data were analyzed by independent sample t test, paired t test, Pearson and Spearman correlation analysis. Results: (1) the expression of serum CCL19 in patients with SLE [(596.25 卤409.19) ng/L and (422.90 卤395.84) ng/L] was significantly higher than that in healthy controls [(157.79 卤125.23) ng/L,P 0.001]. The expression level of serum CCL19 in the first treatment group was higher than that in the treated group (P0.05). (2) the expression of serum CCL19 in SLE patients was positively correlated with the levels of anti-double-stranded deoxyribonucleic acid (double-stranded deoxyribonucleic acid,ds DNA) antibody and anti-nucleosome antibody (anti-nucleosome antibody,Anu A) (r = 0.38, P 0.007, respectively). There was a positive correlation between the level of immunoglobulin Ig Agna Ig G G M and the level of immunoglobulin A G G M (r = 0.30%, P = 0.31%, P = 0.46 9, P = 0.0001, respectively), and the level of immunoglobulin A (Ig) was positively correlated with the level of immunoglobulin G M (P < 0.05). (3) SLE had light hypersensitivity, and the levels of serum CCL19 expression in patients with arthritis and secondary Sjogren's syndrome [(562.25 卤399.12) ng/L, (565.6 卤435.24) ng/L and (694.9 卤531.02) ng/L] were higher than those in non-allergic patients. The levels of SLE in patients without arthritis and Sjogren's syndrome were (394.7 卤281.42) ng/L, (385.90 卤325.33) ng/L and (424.8 卤305.46) ng/L, respectively (P 0.05). (4) the level of serum CCL19 was positively correlated with the proportion of peripheral blood CD27-B cells and CD27-Ig D- double negative memory B cells (r = 0. 519, P < 0. 007, respectively); There was a negative correlation between the ratio of CD27 memory B cells and CD27 Ig D- transformed memory B cells (r = 0. 443 3, P < 0. 027 ~ 0. 616 P ~ (0. 001), and a negative correlation was found between the CD27 memory B cells and the CD27 Ig D- transformed B cells (r = 0. 443 3, P = 0. 027, P = 0. 616). Conclusion: the high expression of CCL19, in serum of patients with SLE is significantly correlated with the production of autoantibodies. CCL19 may be involved in the pathogenesis of SLE through the homeostasis affecting the distribution of B cell subsets.
【作者单位】： 北京大学人民医院风湿免疫科;北京大学国际医院风湿免疫科;
【基金】：国家自然科学基金(81501396、81302554、31470039、81202343、81401341)资助~~
【分类号】：R593.241
本文编号：2398490
[Abstract]:Objective: to detect the expression of chemokine ligand 19 (C-C chemokine ligand 19 CCL19) in the serum of patients with systemic lupus erythematosus (systemic lupus erythematosus,SLE), and to analyze the relationship between the expression of C-C chemokine ligand 19 and the clinical and laboratory parameters of SLE. To explore the possible role of CCL19 in the pathogenesis of SLE. Methods: enzyme linked immunosorbent assay (enzyme linked immunosorbent assay,ELISA) was used to detect 90 patients with SLE (15 patients without glucocorticoid and immunosuppressant therapy). The expression of CCL19 in serum of 75 patients who had been treated and 30 healthy controls were analyzed. The correlation between serum CCL19 level and clinical features and laboratory indexes in patients with SLE was analyzed. Flow cytometry was used to detect the proportion of B cells and their subsets in patients with SLE, and the correlation between serum CCL19 levels and B cells and their subsets was analyzed. The data were analyzed by independent sample t test, paired t test, Pearson and Spearman correlation analysis. Results: (1) the expression of serum CCL19 in patients with SLE [(596.25 卤409.19) ng/L and (422.90 卤395.84) ng/L] was significantly higher than that in healthy controls [(157.79 卤125.23) ng/L,P 0.001]. The expression level of serum CCL19 in the first treatment group was higher than that in the treated group (P0.05). (2) the expression of serum CCL19 in SLE patients was positively correlated with the levels of anti-double-stranded deoxyribonucleic acid (double-stranded deoxyribonucleic acid,ds DNA) antibody and anti-nucleosome antibody (anti-nucleosome antibody,Anu A) (r = 0.38, P 0.007, respectively). There was a positive correlation between the level of immunoglobulin Ig Agna Ig G G M and the level of immunoglobulin A G G M (r = 0.30%, P = 0.31%, P = 0.46 9, P = 0.0001, respectively), and the level of immunoglobulin A (Ig) was positively correlated with the level of immunoglobulin G M (P < 0.05). (3) SLE had light hypersensitivity, and the levels of serum CCL19 expression in patients with arthritis and secondary Sjogren's syndrome [(562.25 卤399.12) ng/L, (565.6 卤435.24) ng/L and (694.9 卤531.02) ng/L] were higher than those in non-allergic patients. The levels of SLE in patients without arthritis and Sjogren's syndrome were (394.7 卤281.42) ng/L, (385.90 卤325.33) ng/L and (424.8 卤305.46) ng/L, respectively (P 0.05). (4) the level of serum CCL19 was positively correlated with the proportion of peripheral blood CD27-B cells and CD27-Ig D- double negative memory B cells (r = 0. 519, P < 0. 007, respectively); There was a negative correlation between the ratio of CD27 memory B cells and CD27 Ig D- transformed memory B cells (r = 0. 443 3, P < 0. 027 ~ 0. 616 P ~ (0. 001), and a negative correlation was found between the CD27 memory B cells and the CD27 Ig D- transformed B cells (r = 0. 443 3, P = 0. 027, P = 0. 616). Conclusion: the high expression of CCL19, in serum of patients with SLE is significantly correlated with the production of autoantibodies. CCL19 may be involved in the pathogenesis of SLE through the homeostasis affecting the distribution of B cell subsets.
【作者单位】： 北京大学人民医院风湿免疫科;北京大学国际医院风湿免疫科;
【基金】：国家自然科学基金(81501396、81302554、31470039、81202343、81401341)资助~~
【分类号】：R593.241
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