Expression levels and clinical significance of serum angiotensinogen and amyloid 4 in patients with rheumatoid arthritis
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摘要:目的
探讨血清血管紧张素原(AGT)、淀粉样蛋白4(SAA4)在类风湿关节炎(RA)患者中的表达水平及临床意义。
方法选取43例活动期RA患者(活动期组)和37例缓解期RA患者(缓解期组)为研究对象，并选取同期40例主诉关节疼痛、肿痛的患者(非RA组)和43例体检健康者(对照组)为对照。检测各组血清AGT、SAA4和炎性因子C反应蛋白(CRP)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)水平。采用Pearson相关检验分析RA患者血清AGT、SAA4与炎性因子的相关性; 采用多因素Logistic回归模型分析血清AGT、SAA4水平与RA发生的关系; 采用受试者工作特征(ROC)曲线分析血清AGT、SAA4水平对RA的诊断价值。
结果活动期组、缓解期组血清AGT、SAA4、CRP、TNF-α、IL-6水平、28项疾病活动度评分(DAS28)高于非RA组和对照组，活动期组血清AGT、SAA4、CRP、TNF-α、IL-6水平、DAS28评分高于缓解期组，差异均有统计学意义(P < 0.05)。Pearson相关检验显示, RA患者血清AGT、SAA4与DAS28评分、CRP、TNF-α、IL-6呈正相关(P < 0.05)。多因素Logistic回归分析显示, AGT、SAA4升高是RA发生的独立危险因素[OR(95%CI)分别为1.247(1.108~1.405)、1.131(1.042~1.227)]。ROC曲线显示，血清AGT、SAA4单独与联合诊断RA的曲线下面积及其95%CI[AUC(95%CI)]分别为0.724(0.501~0.953)、0.778(0.600~0.932)、0.862(0.773~0.925)。
结论RA患者血清AGT、SAA4水平升高与疾病活动性和炎性因子密切相关，联合检测血清AGT、SAA4水平对RA的诊断价值较高。
Abstract:ObjectiveTo investigate the expression level and clinical significance of serum angiotensinogen (AGT) and amyloid 4 (SAA4) in patients with rheumatoid arthritis (RA).
MethodsA total of 43 RA patients in active period (active group) and 37 RA patients in remission period (remission group) were selected as research objects, and 40 patients with joint pain and swelling (non-RA group) and 43 healthy volunteers (control group) were selected as controls. Levels of serum AGT, SAA4 and inflammatory factors such as C reactive protein (CRP), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were detected in all the groups. Pearson correlation test was used to analyze the correlations of serum AGT and SAA4 with inflammatory factors in RA patients; the multivariate Logistic regression model was used to analyze the relationships of serum AGT and SAA4 with the occurrence of RA; the receiver operating characteristic (ROC) curve was used to analyze the values of serum AGT and SAA4 levels in diagnosing RA.
ResultsLevels of serum AGT, SAA4, CRP, TNF-α and IL-6 and the Disease Activity Score-28 items (DAS28) score in the active and the remission groups were significantly higher than those in the non-RA and the control groups, and levels of serum AGT, SAA4, CRP, TNF-α and IL-6 and DAS28 in the active group were also significantly higher than those in the remission group (P < 0.05). Pearson correlation test showed that serum AGT and SAA4 were positively correlated with DAS28, CRP, TNF-α and IL-6 in RA patients (P < 0.05). Multivariate Logistic regression analysis showed that increased AGT and SAA4 were the independent risk factors for the occurrence of RA [OR(95%CI) were 1.247(1.108 to 1.405) and 1.131(1.042 to 1.227) respectively]. ROC curve analysis showed that the areas under the curve and its 95%CI [AUC(95%CI)] of serum AGT and SAA4 alone and their combination for the diagnosis of RA were 0.724(0.501 to 0.953), 0.778(0.600 to 0.932) and 0.862(0.773 to 0.925) respectively.
ConclusionThe elevated levels of serum AGT and SAA4 in RA patients are closely related to disease activity and inflammatory factors, and combined detection of serum AGT and SAA4 levels has high diagnostic value for RA.
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Keywords:
- rheumatoid arthritis /
- angiotensinogen /
- serum amyloid 4 /
- inflammatory factors
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表 1 4组血清AGT、SAA4水平比较(x±s) [M(P25, P75)]
ng/mL 组别 n AGT SAA4 活动期组 43 3.89±0.94*# 9.20(7.08, 11.21)*# 缓解期组 37 2.80±0.89* 5.82(3.45, 8.98)* 非RA组 40 2.48±0.29 4.85(4.30, 5.48) 对照组 43 2.43±0.37 4.89(4.24, 5.33) AGT: 血管紧张素原; SAA4: 血清淀粉样蛋白4。
与对照组、非RA组比较, *P < 0.05;
与缓解期组比较, #P < 0.05。
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表 2 4组炎性因子水平比较(x±s)[M(P25, P75)]
组别 n CRP/(mg/L) TNF-α/(pg/mL) IL-6/(pg/mL) DAS28评分/分 活动期组 43 26.47(16.66, 54.25)*# 127.56±28.62*# 34.52±9.55*# 4.13±0.83*# 缓解期组 37 10.02(3.40, 28.17)* 89.43±27.29* 23.80±7.77* 1.67±0.54* 非RA组 40 3.06(2.16, 4.32) 59.93±16.67 6.79±2.17 0.78±0.26 对照组 43 3.22(2.20, 4.20) 59.47±14.27 6.25±2.15 — CRP: C反应蛋白; TNF-α: 肿瘤坏死因子-α; IL-6: 白细胞介素-6。
与对照组、非RA组比较, *P < 0.05; 与缓解期组比较, #P < 0.05。
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表 3 RA患者血清AGT、SAA4与DAS28评分和炎性因子的相关性
因素 AGT SAA4 r P r P DAS28评分 0.517 < 0.001 0.509 < 0.001 CRP 0.462 < 0.001 0.457 < 0.001 TNF-α 0.403 < 0.001 0.512 < 0.001 IL-6 0.387 0.002 0.501 < 0.001
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表 4 血清AGT、SAA4水平与RA发生的多因素Logistic回归分析
指标/因素 β SE Wald χ2 P OR(95%CI) 常数 -0.065 0.029 5.001 0.025 — CRP升高 0.329 0.121 7.432 0.006 1.390 (1.097~1.760) TNF-α升高 0.026 0.009 9.304 0.002 1.026 (1.009~1.044) IL-6升高 0.085 0.024 12.188 < 0.001 1.089 (1.038~1.142) AGT升高 0.221 0.061 13.301 < 0.001 1.247 (1.108~1.405) SAA4升高 0.123 0.042 8.672 0.003 1.131 (1.042~1.227)
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表 5 血清AGT、SAA4水平单独与联合诊断RA的价值
指标 AUC(95%CI) 阈值 灵敏度 特异度 约登指数 准确度 AGT 0.724(0.501~0.953) 3.0 ng/mL 0.700 0.750 0.450 0.717 SAA4 0.778(0.600~0.932) 6.1 ng/mL 0.725 0.775 0.500 0.742 二者联合 0.862(0.773~0.925) 1.4 0.825 0.850 0.675 0.833
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