风湿病与关节炎
風濕病與關節炎
풍습병여관절염
Rheumatism and Arthritis
2015年
5期
13-17
,共5页
脊柱炎,强直性%血清%Dkk-1%骨化%影像学%疾病活动度%炎症指标%益赛普
脊柱炎,彊直性%血清%Dkk-1%骨化%影像學%疾病活動度%炎癥指標%益賽普
척주염,강직성%혈청%Dkk-1%골화%영상학%질병활동도%염증지표%익새보
spondylitis,ankylosing%serum%Dkk-1%ossification%iconography%disease activity degree%inlfammation index%Yisaipu
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（mSASSS）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·mL-1低于对照组（98.0±27.6）pg·mL-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·mL-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·mL-1（P <0.01）。ROC曲线分析显示，Dkk-1水平69.75pg·mL-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mSASSS评分在基线状态和治疗后差异无统计学意义（P >0.01），且mSASSS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。
目的：探討彊直性脊柱炎患者血清Dickkopf-1（Dkk-1）的水平及其診斷價值，瞭解Dkk-1與彊直性脊柱炎炎癥及放射學進展的關繫。方法：選取接受註射用重組人Ⅱ型腫瘤壞死因子受體-抗體融閤蛋白（益賽普）治療的彊直性脊柱炎患者55例為彊直性脊柱炎組，同期45例健康體檢者作為對照組。隨訪2年，分彆在基線狀態、治療24箇月時評估彊直性脊柱炎患者各項臨床指標[年齡、性彆、疾病活動度（BASFI、BASDAI、BASMI、BASRI）]、影像學進展（mSASSS）以及炎癥指標[紅細胞沉降率（ESR）、C-反應蛋白（CRP）]。採用ELISA法檢測彊直性脊柱炎患者血清Dkk-1濃度。運用相關分析法分析Dkk-1與疾病活動度、影像學進展及炎癥指標的關繫。結果：彊直性脊柱炎組在基線狀態時，ESR及血清CRP水平高于對照組，但Dkk-1濃度（72.6±19.5）pg·mL-1低于對照組（98.0±27.6）pg·mL-1（P <0.01）；彊直性脊柱炎組在治療24箇月時，ESR及血清CRP水平較基線狀態時明顯下降（P <0.01），治療24箇月時，BASFI、BASMI和BASDI評分較基線狀態時明顯改善（P <0.01），但在治療24箇月時，Dkk-1濃度為（74.2±15.3）pg·mL-1，較基線狀態時稍有升高（P=0.57），仍低于對照組（98.0±27.6）pg·mL-1（P <0.01）。ROC麯線分析顯示，Dkk-1水平69.75pg·mL-1為截斷點，該點診斷的敏感度為84.02％，特異度為91.50％，麯線下麵積（AUC）為0.94，診斷效力高。相關分析顯示，彊直性脊柱炎組患者在基線狀態時和治療24箇月時，血清Dkk-1水平與ESR、CRP、BASFI、BASMI以及BASDAI評分無明顯相關性。而放射學指數BASRI及影像學mSASSS評分在基線狀態和治療後差異無統計學意義（P >0.01），且mSASSS評分與Dkk-1水平在基線狀態和治療24箇月時呈顯著負相關（r=-0.78，P <0.01）。結論：腫瘤壞死因子拮抗劑對彊直性脊柱炎患者血清Dkk-1水平無明顯改善，血清Dkk-1水平與放射學變化明顯相關，提示血清Dkk-1的產生可能與炎癥狀態無明顯相關性，Dkk-1可能參與瞭彊直性脊柱炎的骨化形成；腫瘤壞死因子拮抗劑可能對彊直性脊柱炎骨化進程無明顯阻止作用，彊直性脊柱炎患者血清Dkk-1可作為一種新的反映骨化指標及影像學進展的血清生物標誌物。
목적：탐토강직성척주염환자혈청Dickkopf-1（Dkk-1）적수평급기진단개치，료해Dkk-1여강직성척주염염증급방사학진전적관계。방법：선취접수주사용중조인Ⅱ형종류배사인자수체-항체융합단백（익새보）치료적강직성척주염환자55례위강직성척주염조，동기45례건강체검자작위대조조。수방2년，분별재기선상태、치료24개월시평고강직성척주염환자각항림상지표[년령、성별、질병활동도（BASFI、BASDAI、BASMI、BASRI）]、영상학진전（mSASSS）이급염증지표[홍세포침강솔（ESR）、C-반응단백（CRP）]。채용ELISA법검측강직성척주염환자혈청Dkk-1농도。운용상관분석법분석Dkk-1여질병활동도、영상학진전급염증지표적관계。결과：강직성척주염조재기선상태시，ESR급혈청CRP수평고우대조조，단Dkk-1농도（72.6±19.5）pg·mL-1저우대조조（98.0±27.6）pg·mL-1（P <0.01）；강직성척주염조재치료24개월시，ESR급혈청CRP수평교기선상태시명현하강（P <0.01），치료24개월시，BASFI、BASMI화BASDI평분교기선상태시명현개선（P <0.01），단재치료24개월시，Dkk-1농도위（74.2±15.3）pg·mL-1，교기선상태시초유승고（P=0.57），잉저우대조조（98.0±27.6）pg·mL-1（P <0.01）。ROC곡선분석현시，Dkk-1수평69.75pg·mL-1위절단점，해점진단적민감도위84.02％，특이도위91.50％，곡선하면적（AUC）위0.94，진단효력고。상관분석현시，강직성척주염조환자재기선상태시화치료24개월시，혈청Dkk-1수평여ESR、CRP、BASFI、BASMI이급BASDAI평분무명현상관성。이방사학지수BASRI급영상학mSASSS평분재기선상태화치료후차이무통계학의의（P >0.01），차mSASSS평분여Dkk-1수평재기선상태화치료24개월시정현저부상관（r=-0.78，P <0.01）。결론：종류배사인자길항제대강직성척주염환자혈청Dkk-1수평무명현개선，혈청Dkk-1수평여방사학변화명현상관，제시혈청Dkk-1적산생가능여염증상태무명현상관성，Dkk-1가능삼여료강직성척주염적골화형성；종류배사인자길항제가능대강직성척주염골화진정무명현조지작용，강직성척주염환자혈청Dkk-1가작위일충신적반영골화지표급영상학진전적혈청생물표지물。
[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-1was 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 serum level 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 > 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.
