摘要
目的:探讨强直性脊柱炎患者血清Dickkopf-1(Dkk-1)的水平及其诊断价值,了解Dkk-1与强直性脊柱炎炎症及放射学进展的关系。方法:选取接受注射用重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白(益赛普)治疗的强直性脊柱炎患者55例为强直性脊柱炎组,同期45例健康体检者作为对照组。随访2年,分别在基线状态、治疗24个月时评估强直性脊柱炎患者各项临床指标[年龄、性别、疾病活动度(BASFI、BASDAI、BASMI、BASRI)]、影像学进展(m SASSS)以及炎症指标[红细胞沉降率(ESR)、C-反应蛋白(CRP)]。采用ELISA法检测强直性脊柱炎患者血清Dkk-1浓度。运用相关分析法分析Dkk-1与疾病活动度、影像学进展及炎症指标的关系。结果:强直性脊柱炎组在基线状态时,ESR及血清CRP水平高于对照组,但Dkk-1浓度(72.6±19.5)pg·m L-1低于对照组(98.0±27.6)pg·m L-1(P<0.01);强直性脊柱炎组在治疗24个月时,ESR及血清CRP水平较基线状态时明显下降(P<0.01),治疗24个月时,BASFI、BASMI和BASDI评分较基线状态时明显改善(P<0.01),但在治疗24个月时,Dkk-1浓度为(74.2±15.3)pg·m L-1,较基线状态时稍有升高(P=0.57),仍低于对照组(98.0±27.6)pg·m L-1(P<0.01)。ROC曲线分析显示,Dkk-1水平69.75 pg·m L-1为截断点,该点诊断的敏感度为84.02%,特异度为91.50%,曲线下面积(AUC)为0.94,诊断效力高。相关分析显示,强直性脊柱炎组患者在基线状态时和治疗24个月时,血清Dkk-1水平与ESR、CRP、BASFI、BASMI以及BASDAI评分无明显相关性。而放射学指数BASRI及影像学m SASSS评分在基线状态和治疗后差异无统计学意义(P>0.01),且m SASSS评分与Dkk-1水平在基线状态和治疗24个月时呈显著负相关(r=-0.78,P<0.01)。结论:肿瘤坏死因子拮抗剂对强直性脊柱炎患者血清Dkk-1水平无明显改善,血清Dkk-1水平与放射学变化明显相关,提示血清Dkk-1的产生可能与炎症状态无明显相关性,Dkk-1可能参与了强直性脊柱炎的骨化形成;肿瘤坏死因子拮抗剂可能对强直性脊柱炎骨化进程无明显阻止作用,强直性脊柱炎患者血清Dkk-1可作为一种新的反映骨化指标及影像学进展的血清生物标志物。
[ABSTRACT]Objective：To investigate the serum Dkk-1 level and its diagnostic value in patients with ankylosing spondylitis to learn the relationship between Dkk-1 and bone imaging changes.Methods：Chose 55 cases of ankylosing spondylitis treated with Yisaipu（Recombinant Human Tumor Necrosis Factor-α Re-ceptorⅡ：Igg Fc Fusion Protein） as the ankylosing spondylitis group,and 45 healthy subjects as the control group.During the 2 years of follow-up,evaluated,respectively atbaseline and after 24 months of treatment,the clinical index（age,gender,disease activity：BASFI,BASDAI,BAS-MI,BASRI）,radiographic progression（mSASSS） and inlfammatory index （ESR,CRP） of the patients with ankylosing spondylitis.ELISA method was used to detect serum Dkk-1 concentration of ankylosing spondylitis patients.Relative analysis Methods were used to analyze the relationship between Dkk-1 and disease activity, radiographic progression and inflammatory biomarkers.Results：ESR and serum CRP levels of the ankylos-ing spondylitis group were higher than those of the control group at the baseline,but the concentration of Dkk-1 （72.6±19.5） pg·mL^-1 was lower than that of the control group（98.0±27.6） pg·mL^-1（P 〈 0.01）.At the 24 th month of treatment,ESR and serum CRP level of the ankylosing spondylitis group signiifcantly decreased （P 〈 0.01） than those of at the baseline,while BASFI,BASMI and BASDI were signiifcantly improved（P 〈 0.01） compared with those at the baseline.After 24 months of treatment,the concentration of Dkk-1（74.2±15.3）pg·mL^-1 was slightly increased（P = 0.57） compared with that at the baseline,but still lower than the control group （98.0 ± 27.6）pg·mL^-1（P 〈 0.01）.ROC curve analysis showed that the level of Dkk-1（69.75 pg·mL^-1） was the cut-off point,whose diagnostic sensitivity was 84.02%,speciifcity was 91.50%,and area under curve （AUC） was 0.94,with high efifciency of diagnosis.Correlation analysis showed that at the baseline and after 24 months of treat-ment,there was no signiifcant correlation between the serumLevel of Dkk-1 and ESR,CRP,BASFI,BASMI and BAS-DAI.The BASRI and mSASSS score had no signiifcant differences at the baseline and after treatment（P ＆gt; 0.05）, and there was a signiifcant negative correlation（r =-0.78,P 〈 0.01） between the scores of mSASSS and the Dkk-1 levels at the baseline and after 24 months of treatment.Conclusion：Tumor necrosis factor antagonist cannot significantly improve serum Dkk-1 level in patients with ankylosing spondylitis,and the level of serum Dkk-1 cor-relates with the radiographic changes,suggesting that the generation of serum Dkk-1 has no significant correlation with the inlfammatory state,and Dkk-1 may be involved in ankylosing spondylitis ossiifcation.Tumor necrosis factor antagonist may have no obvious preventive effect on the ossification process,and serum Dkk-1 in patients with an-kylosing spondylitis can be regarded as a biomarker to reflect the ossification indexes and iconographical progress.
出处
《风湿病与关节炎》
2015年第5期13-17,共5页
Rheumatism and Arthritis
基金
国家自然基金(30600560)
江苏省六大人才高峰基金(WSN-051)
