發(fā)布時(shí)間：2019-01-02 12:33

【摘要】：目的:檢測(cè)趨化因子配體19(C-C chemokine ligand 19,CCL19)在系統(tǒng)性紅斑狼瘡(systemic lupus erythematosus,SLE)患者血清中的表達(dá),并分析其與SLE患者臨床和實(shí)驗(yàn)室指標(biāo)的關(guān)系,探討CCL19在SLE發(fā)病機(jī)制中的可能作用。方法:采用酶聯(lián)免疫吸附試驗(yàn)(enzyme linked immunosorbent assay,ELISA)法檢測(cè)90例SLE患者(未接受過糖皮質(zhì)激素和免疫抑制劑治療的初治患者15例,曾治療過的患者75例)和30名健康對(duì)照血清中CCL19的表達(dá)水平,分析SLE患者血清CCL19水平與臨床特征和實(shí)驗(yàn)室指標(biāo)的相關(guān)性。利用流式細(xì)胞術(shù)檢測(cè)SLE患者B細(xì)胞及其亞群的比例,并進(jìn)行血清CCL19水平與B細(xì)胞及其亞群比例的相關(guān)性分析。數(shù)據(jù)分析采用獨(dú)立樣本t檢驗(yàn)、配對(duì)t檢驗(yàn)、Pearson和Spearman相關(guān)分析。結(jié)果:(1)SLE初治患者和經(jīng)治患者血清CCL19表達(dá)水平[分別為(596.25±409.19)ng/L和(422.90±395.84)ng/L]顯著高于健康對(duì)照組[(157.79±125.23)ng/L,P均0.001],初治患者組血清CCL19表達(dá)水平又高于經(jīng)治患者組(P0.05);(2)SLE患者血清CCL19表達(dá)水平與抗雙鏈脫氧核糖核酸(double-stranded deoxyribonucleic acid,ds DNA)抗體、抗核小體抗體(anti-nucleosome antibody,Anu A)水平呈正相關(guān)(分別為r=0.38,P=0.007;r=0.332,P=0.029),與免疫球蛋白Ig A、Ig G、Ig M水平呈正相關(guān)(分別為r=0.30,P=0.005;r=0.31,P=0.003;r=0.469,P=0.0001);(3)SLE有光過敏、關(guān)節(jié)炎和繼發(fā)干燥綜合征患者血清CCL19表達(dá)水平[分別為(562.25±399.12)ng/L、(565.6±435.24)ng/L和(694.9±531.02)ng/L]分別較無光過敏、無關(guān)節(jié)炎和未繼發(fā)干燥綜合征SLE患者高[分別為(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水平與外周血CD27-B細(xì)胞和CD27-Ig D-雙陰性記憶性B細(xì)胞的比例呈正相關(guān)(分別為r=0.519,P=0.007;r=0.461,P=0.018),與CD27+記憶性B細(xì)胞和CD27+Ig D-轉(zhuǎn)化后記憶性B細(xì)胞的比例呈負(fù)相關(guān)(分別為r=-0.433,P=0.027;r=-0.616,P=0.001)。結(jié)論:SLE患者血清中高表達(dá)CCL19,與自身抗體的產(chǎn)生顯著相關(guān),CCL19可能通過影響B(tài)細(xì)胞亞群分布的內(nèi)穩(wěn)態(tài)參與SLE發(fā)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 鹵409.19) ng/L and (422.90 鹵395.84) ng/L] was significantly higher than that in healthy controls [(157.79 鹵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 鹵399.12) ng/L, (565.6 鹵435.24) ng/L and (694.9 鹵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 鹵281.42) ng/L, (385.90 鹵325.33) ng/L and (424.8 鹵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.
【作者單位】： 北京大學(xué)人民醫(yī)院風(fēng)濕免疫科;北京大學(xué)國際醫(yī)院風(fēng)濕免疫科;
【基金】：國家自然科學(xué)基金(81501396、81302554、31470039、81202343、81401341)資助~~
【分類號(hào)】：R593.241

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