Clinical significance of angiogenin protein 4, interleukin-17 and nuclear factor-kappa B ligand in serum and articular fluid of patients with rheumatoid arthritis
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摘要:目的
探讨类风湿关节炎患者血清及关节液血管生成素样蛋白4(ANGPTL4)、白细胞介素-17(IL-17)、核因子κB受体活化因子配体(RANKL)的表达水平及其临床意义。
方法选取165例类风湿关节炎患者纳入观察组，选取同期165例骨关节炎患者纳入疾病对照组，并选取165名健康体检者纳入正常对照组。采用酶联免疫吸附法检测3组研究对象血清和(或)关节液中ANGPTL4、IL-17、RANKL表达水平，分析观察组患者血清ANGPTL4、IL-17、RANKL水平与疾病活动度的相关性。
结果观察组血清ANGPTL4、IL-17、RANKL水平高于疾病对照组和正常对照组，疾病对照组血清ANGPTL4、IL-17、RANKL水平高于正常对照组，差异均有统计学意义(P＜0.05)。观察组关节液ANGPTL4、IL-17、RANKL表达水平与疾病对照组比较，差异无统计学意义(P＞0.05); 观察组和疾病对照组关节液ANGPTL4、IL-17、RANKL表达水平均低于血清表达水平，差异有统计学意义(P＜0.05)。观察组不同疾病活动度患者中，高度活动者血清ANGPTL4、IL-17、RANKL水平高于低度活动者、中度活动者，且中度活动者高于低度活动者，差异均有统计学意义(P＜0.05)。Pearson相关分析显示，类风湿关节炎患者血清ANGPTL4、IL-17、RANKL水平均与疾病活动度指标28个关节疾病活动度(DAS28)评分、红细胞沉降率(ESR)、C反应蛋白(CRP)水平呈正相关(P＜0.001)。受试者工作特征曲线显示，血清ANGPTL4、IL-17、RANKL联合预测类风湿关节炎患者1年关节影像学进展的曲线下面积为0.910。
结论类风湿关节炎患者血清ANGPTL4、IL-17、RANKL与疾病活动度均呈正相关，三者联合预测1年关节影像学进展的效能较好，为监测类风湿关节炎病情变化提供了新途径。
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关键词:
- 类风湿关节炎 /
- 血管生成素样蛋白4 /
- 白细胞介素-17 /
- 核因子-κB受体活化因子配体 /
- 疾病活动度
Abstract:ObjectiveTo explore the clinical significance and expression levels of angiogenin protein 4(ANGPTL4), interleukin-17(IL-17) and receptor activator of nuclear factor-kappa B ligand (RANKL) in serum and joint fluid of patients with rheumatoid arthritis.
MethodsA total of 165 patients with rheumatoid arthritis were selected as observation group, 165 patients with osteoarthritis during the same period were selected as disease control group, and another 165 healthy physical examination subjects as normal control group. The expressions of ANGPTL4, IL-17 and RANKL in serum and(or) joint fluid of the observation group, normal control group and disease control group were detected by enzyme linked immunosorbent assay. The correlations of the levels of ANGPTL4, IL-17 and RANKL in serum of the observation group with disease activity were analyzed.
ResultsThe serum levels of ANGPTL4, IL-17 and RANKL in the observation group were higher than those of the disease control group and the normal control group, while the ANGPTL4, IL-17 and RANKL in the disease control group were higher than the normal control group (P < 0.05). There was no significant difference in the expression levels of ANGPTL4, IL-17 and RANKL in the joint fluid between the observation group and the disease control group (P > 0.05). The expression levels of ANGPTL4, IL-17 and RANKL in the joint fluid of the observation group and the disease control group were lower than those in the serum, and the differences were statistically significant (P < 0.05). In patients with different disease activity degree in the observation group, the serum levels of ANGPTL4, IL-17 and RANKL in the highly active patients were higher than those in the low and moderate activity degree patients, and were higher in the moderate activity degree patients than those in the low activity degree patients, and the differences were statistically significant (P < 0.05). Pearson correlation analysis showed that serum ANGPTL4, IL-17 and RANKL levels were positively correlated with Disease Activity Score in 28 joints (DAS28) score, erythrocyte sedimentation rate(ESR) and C-reactive protein(CRP) levels(P < 0.001). Receiver operating characteristic curve showed that the area under the curve of ANGPTL4, IL-17 and RANKL in combination in predicting the 1-year joint imaging progression in patients with rheumatoid arthritis was 0.910.
ConclusionSerum levels of ANGPTL4, IL-17 and RANKL are significantly positively correlated with disease activity degree in patients with rheumatoid arthritis, their combined prediction of 1-year joint imaging progression has better efficacy, providing a new way to monitor the changes of rheumatoid arthritis.
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表 1 3组一般资料比较(x±s)[n(%)]
组别 n 性别 年龄/岁 体质量指数/(kg/m2) 病程/月 男 女 正常对照组 165 44(26.67) 121(73.33) 52.76±5.03 22.76±1.15 — 疾病对照组 165 45(27.27) 120(72.73) 52.06±4.98 22.98±1.31 34.61±9.07 观察组 165 43(26.06) 122(73.94) 52.55±5.01 22.89±1.29 36.42±8.74 
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表 2 3组血清ANGPTL4、IL-17、RANKL表达水平比较(x±s)
组别 n ANGPTL4/(ng/mL) IL-17/(pg/mL) RANKL/(pg/mL) 正常对照组 165 2.65±0.72 4.84±1.13 81.24±4.63 疾病对照组 165 7.89±2.17* 9.56±3.72* 126.93±12.77* 观察组 165 15.64±5.43*# 22.48±6.95*# 212.25±25.78*# ANGPTL4: 血管生成素样蛋白4; IL-17: 白细胞介素-17; RANKL: 核因子κB受体活化因子配体。
与正常对照组比较, *P＜0.05; 与疾病对照组比较, #P＜0.05。
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表 3 观察组与疾病对照组血液、关节液中ANGPTL4、IL-17、RANKL表达水平比较(x±s)
组别 n 样本 ANGPTL4/(ng/mL) IL-17/(pg/mL) RANKL/(pg/mL) 疾病对照组 165 关节液 3.42±1.11* 4.57±1.27* 95.61±8.71* 血清 7.89±2.17 9.56±3.72 126.93±12.77 观察组 165 关节液 3.65±1.37* 4.79±1.54* 97.32±9.56* 血清 15.64±5.43# 22.48±6.95# 212.25±25.78# ANGPTL4: 血管生成素样蛋白4; IL-17: 白细胞介素-17; RANKL: 核因子κB受体活化因子配体。
与血清比较, *P＜0.05; 与疾病对照组比较, #P＜0.05。
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表 4 观察组不同疾病活动度患者血清ANGPTL4、IL-17、RANKL水平比较(x±s)
组别 n ANGPTL4/(ng/mL) IL-17/(pg/mL) RANKL/(pg/mL) 低度活动组 80 11.37±3.82 7.94±2.56 101.42±9.86 中度活动组 42 15.45±5.64* 20.82±5.53* 200.53±18.57* 高度活动组 43 20.83±8.91*# 27.91±8.72*# 261.86±31.29*# ANGPTL4: 血管生成素样蛋白4; IL-17: 白细胞介素-17; RANKL: 核因子κB受体活化因子配体。
与低度活动组比较, *P＜0.05; 与中度活动组比较, #P＜0.05。
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表 5 血清ANGPTL4、IL-17、RANKL与疾病活动度指标的相关性分析
指标 DAS28评分 ESR CRP r P r P r P ANGPTL4 0.562 ＜0.001 0.748 ＜0.001 0.718 ＜0.001 IL-17 0.618 ＜0.001 0.705 ＜0.001 0.842 ＜0.001 RANKL 0.584 ＜0.001 0.691 ＜0.001 0.803 ＜0.001 DAS28: 28个关节疾病活动度; ESR: 红细胞沉降率; CRP: C反应蛋白; ANGPTL4: 血管生成素样蛋白4;
IL-17: 白细胞介素-17; RANKL: 核因子κB受体活化因子配体。
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