血清骨桥蛋白在类风湿关节炎患者血清中的表达及临床意义

The expression and clinical significance of serum osteopontin in patients with rheumatoid arthritis

目的探讨骨桥蛋白(OPN)在类风湿关节炎(RA)患者血清中的表达水平及其临床意义。方法选择68例RA患者作为RA组和63例体检的健康者作为对照组,并将RA组分为骨侵蚀组(39例)和非骨侵蚀组(29例)。根据血清抗CCP抗体情况将RA组分为抗CCP抗体阴性组和阳性组。比较各组血清中OPN、β-CTX、DKK-1、PINP水平,用双能X线吸收测定法检测RA组患者骨密度(包括股骨颈、Ward's三角区);收集比较其他数据。结果(1)RA组OPN(41.86±6.92)ng/mL、β-CTX(825.74±152.76)pg/mL、DKK-1(21.00±3.79)ng/mL较对照组[(24.91±5.20)ng/mL、(482.85±103.47)pg/mL、(11.65±1.73)ng/mL]升高,差异有统计学意义(t分别为15.91、15.14、18.38,P<0.05);而RA组PINP(25.59±7.76)ng/mL较对照组[(47.29±7.00)ng/mL,t=-16.76,P<0.05]降低。(2)骨侵蚀组OPN(45.14±6.45)ng/mL、β-CTX(901.65±135.31)pg/mL、DKK-1(22.38±3.57)ng/mL高于非骨侵蚀组[(37.45±4.80)ng/mL、(723.66±110.35)ng/mL、(19.15±3.29)ng/mL],差异有统计学意义(t分别为5.64、5.79、3.81,P=0.000)。骨侵蚀组PINP(23.68±7.44)ng/mL低于非骨侵蚀组[(28.15±7.56)ng/mL,t=-2.43,P=0.018]。(3)RA抗CCP抗体阴性组OPN(45.11±7.07)ng/mL高于正常对照组(24.91±5.20)ng/mL,差异有统计学意义(t=11.00,P=0.000),而与抗CCP抗体阳性组(40.78±6.59)ng/mL相比较差异无统计学意义(t=2.30,P=0.020)。(4)骨侵蚀组的骨密度(包括股骨颈及Ward's三角区)均低于非骨侵蚀组[(0.61±0.11)g/cm^(2)vs(0.67±0.09)g/cm^(2),t=2.28,P=0.030;(0.43±0.12)g/cm^(2)vs(0.54±0.13)g/cm^(2),t=3.76,P=0.000]。(5)相关性分析显示:OPN与DAS28(ESR)、β-CTX、DKK-1呈正相关(r分别为0.30、0.40、0.37,P<0.05),与PINP呈负相关(r=-0.31,P<0.05),与抗CCP抗体无相关性(r=-0.06,P=0.640)。(6)ROC曲线分析提示血清OPN对RA骨侵蚀及疾病活动度均具有较好的预测价值。结论RA患者血清OPN水平较健康组显著升高,以骨侵蚀组升高更为明显。OPN与骨吸收指标及RA疾病活动度指标呈正相关,提示OPN可能参与RA骨侵蚀过程,并促进RA疾病活动。抗CCP抗体阴性组血清OPN升高,使OPN可能成为诊断RA的另一个生物标志物。

Objective To investigate the expression levels and clinical significance of serum osteopontin in patients with rheumatoid arthritis.Methods Sixty-eight patients with RA were selected as the RA group and sixty-three healthy patients who underwent physical examination as the control group,and the RA group was divided into bone erosion group(39 cases)and non-bone erosion group(29 cases).According to the serum anti-Cyclic citrullinated peptideantibody situation,the RA group was divided into anti-CCP antibody negative group and positive group.The levels of OPN,β-CTX,DKK-1,and PINP in the serum of each group were measured by ELISA method,and bone density(including femoral neck and Ward's triangle)in the RA group was measured by dual-energy X-ray absorption assay;other data were collected and compared.Results(1)The level of OPN(41.86±6.92)ng/mL,β-CTX(825.74±152.76)pg/mL,DKK-1(21.00±3.79)ng/mL in the RA group compared with the control group[(24.91±5.20)ng/mL,(482.85±103.47)pg/mL,(11.65±1.73)ng/mL]were raised,and there were statistical differences(t was15.91,15.14,18.38,respectively,P<0.05).But the level of PINP(25.59±7.76)ng/mL in the RA group was lower than that in the control group[(47.29±7.00)ng/mL,t=-16.76,P<0.05].(2)The level of OPN(45.14±6.45)ng/mL,β-CTX(901.65±135.31)pg/mL,DKK-1(22.38±3.57)ng/mL in the bone erosion group compared with the non-bone erosion group[(37.45±4.80)ng/mL,(723.66±110.35)ng/mL,(19.15±3.29)ng/mL]were raised,and there were statistical differences(t was 5.64,5.79,3.81,respectively,P=0.000).The level of PINP(23.68±7.44)ng/mL in the bone erosion group was lower than that in the non-bone erosion group[(28.15±7.56)ng/mL,t=-2.43,P=0.018].(3)RA anti-CCP antibody negative group OPN(45.11±7.07)ng/mL was higher than that of normal control group(24.91±5.20)ng/mL,with a strong statistical difference(t=11.00,P=0.000),but the difference was small compared with the anti-CCP positive group(40.78±6.59)ng/mL(t=2.30,P=0.020).(4)Bone bone density(including femur neck and Ward's triangle)was lower in the bone erosion group[(0.61±0.11)g/cm^(2)vs(0.67±0.09)g/cm^(2),t=2.28,P=0.030;(0.43±0.12)g/cm^(2)vs(0.54±0.13)g/cm^(2),t=3.76,P=0.000].(5)Correlation analysis showed that OPN was positively correlated with DAS28(ESR),β-CTX,and DKK-1(r was 0.30,0.40,0.37,P<0.05),was negatively correlated with PINP(r=-0.31,P<0.05),and had no correlation with anti-CCP antibodies(r=-0.06,P=0.640).(6)ROC curve analysis suggests that serum OPN has good predictive value for both RA bone erosion and disease activity.Conclusion The serum OPN levels in patients with RA were significantly higher than in the healthy group and more pronounced in the bone erosion group.OPN was positively correlated with bone resorption and RA disease activity,suggesting that OPN may be involved in the RA bone erosion process and promote RA disease activity.The serum OPN is elevated in the anti-CCP-negative group,making OPN another biomarker for diagnosing RA.