系统性红斑狼疮趋化因子CXCL13水平升高的临床意义

Clinical significance of chemokine CXCL13 in systemic lupus erythematosus

目的探讨趋化因子CXCL13在系统性红斑狼疮(systemic lupus erythematosus,SLE患者血浆中的表达及临床意义。方法收集SLE患者60例,健康对照20例,采用酶联免疫吸附法(ELISA)检测两组血浆中CXCL13的表达水平,并分析与SLE患者实验室指标及疾病活动度的关系;同时比较血浆CXCL13水平在狼疮性肾炎(lupus nephritis,LN)和非LN患者间的表达差异;受试者工作特征曲线(ROC曲线)判断血浆CXCL13对诊断LN的敏感性和特异性。采用t检验、Kruskal-Wallis H检验、Pearson相关分析进行统计学数据分析。结果 SLE患者血浆CXCL13为(272. 1±232. 7) pg/ml,明显高于健康对照组(52. 1±31. 0) pg/ml (P <0. 05)。LN患者血浆CXCL13水平为(340. 9±248. 6) pg/ml,明显高于非LN患者[(134. 5±106. 9) pg/ml; Z=3. 895,P <0. 01]。血浆CXCL13水平与SLE患者SLEDAI评分呈正相关(r=0. 267,P <0. 05),与补体C3 (r=-0. 294,P <0. 05)、外周血血红蛋白含量(r=-0. 299,P <0. 05)、血小板计数(r=-0. 300,P <0. 05)、淋巴细胞计数(r=-0. 309,P <0. 05)呈负相关。疾病活动组患者血浆CXCL13水平明显高于疾病稳定组[(335. 7±248. 2) pg/ml比(144. 9±127. 5) pg/ml,t=3. 223,P <0. 01]。抗ds DNA抗体阳性组血浆CXCL13水平明显高于抗ds DNA抗体阴性组[(367. 0±285. 4) pg/ml比(204. 3±158. 6) pg/ml,t=2. 824,P <0. 01]; AHA阳性组血浆CXCL13水平明显高于AHA阴性组[(375. 3±276. 8) pg/ml比(216. 5±186. 3) pg/ml; t=2. 645,P <0. 05]。LN患者血浆CXCL13水平与血清尿素氮呈正相关(r=0. 425,P <0. 01),与e GFR呈负相关(r=-0. 385,P <0. 05)。血浆CXCL13水平≥116. 95 pg/ml,对LN诊断的敏感性为92. 5%,特异性为60. 0%。结论 SLE患者血浆CXCL13水平明显升高,可能与自身抗体产生及血液系统和肾脏系统损害有关,CXCL13可作为判断SLE疾病活动性的指标之一。

Objective To detect the plasma level of chemokine CXCL13 in patients with systemic lupus erythematosus (SLE) and to explore the clinical significance of CXCL13 in SLE. Methods Sixty SLE patients and 20 healthy controls were recruited into this study. Enzyme-linked immunosorbent assay (ELISA) was used to detect plasma chemokine CXCL13 levels in two groups. The relationship between plasma level of CXCL13 and laboratory parameters, and disease activity as well were analyzed in SLE group. The plasma levels of CXCL13 in patients with or without lupus nephritis (LN) were compared. The sensitivity and specificity of plasma levels of CXCL13 in the diagnosis of LN were analyzed by receiver-operating characteristic(ROC)curve. Analysis of variance, t -test, Kruskal-Wallis H test and Pearson’s correlation test were used for statistical analysis. Results The average plasma level of CXCL13 (272.1±232.7 pg/ml) in SLE group was significantly higher than that in healthy controls (52.1±31.0 pg/ml). The average level of plasma CXCL13 were significantly higher in SLE patients with LN (340.9±248.6 pg/ml] than that in patients without LN (134.5±106.9 pg/ml)( Z = 3.895, P <0.01). The levels of plasma CXCL13 in SLE patients showed positive correlation with SLEDAI ( r =0.267, P <0.05), negative correlation with complement C3 ( r =-0.294, P <0.05), hemoglobin ( r =-0.299 , P <0.05), platelet count ( r =-0.300, P <0.05), and lymphocyte count ( r =-0.309, P <0.05). Plasma levels of CXCL13 in active SLE patients were higher than those in stable group (335.7±248.2 pg/ml vs. 144.9±127.5 pg/ml, t =3.223, P <0.01). In addition, the plasma levels of CXCL13 were significantly higher in anti-dsDNA antibody positive group than those in anti-dsDNA antibody negative group (367.0± 285.4 pg/ml vs. 204.3 ±158.6 pg/ml, t =2.824, P <0.01), in AHA positive group than those in AHA negative group (375.3±276.8 pg/ml vs. 216.5±186.3 pg/ml, t =2.645, P <0.05). The plasma CXCL13 levels were positively correlated with blood urea nitrogen ( r =0.425, P <0.01) and negatively correlated with estimated glomerular filtration rate ( r =-0.385, P <0.05) in LN patients. The sensitivity and specificity of plasma CXCL13 in diagnosing LN was 92.5% and 60.0% respectively at a cut-off value of 116.95 pg/ml. Conclusions The average level of CXCL13 was elevated in SLE patients. It may play a role in the autoantibodies production,hematoloogical and renal involvement in SLE. Plasma level of CXCL13 may be used as one of the serological markers in evaluation of SLE activity.