血清骨转换生物标志物与银屑病患者外周和中轴关节炎的发生相关：一项前瞻性横断面比较研究。
Serum bone-turnover biomarkers are associated with the occurrence of peripheral and axial arthritis in psoriatic disease: a prospective cross-sectional comparative study.
机构信息
Department of Rheumatology, Royal National Hospital for Rheumatic Diseases, Bath, UK.
Department of Rheumatology, Cambridge University Hospitals NHSFT, Cambridge, UK.
出版信息
Arthritis Res Ther. 2017 Sep 21;19(1):210. doi: 10.1186/s13075-017-1417-7.
BACKGROUND
A recent systematic review identified four candidate serum-soluble bone-turnover biomarkers (dickkopf-1, Dkk-1; macrophage-colony stimulating factor, M-CSF; matrix metalloproteinase-3, MMP-3; osteoprotegerin, OPG) showing possible association with psoriatic arthritis (PsA). We aimed to: (i) confirm and determine if these four biomarkers are associated with PsA; (ii) differentiate psoriasis cases with and without arthritis; and (iii) differentiate PsA cases with and without axial arthritis.
METHODS
A prospective cross-sectional comparative two-centre study recruited 200 patients with psoriasis without arthritis (PsC), 127 with PsA without axial arthritis (pPsA), 117 with PsA with axial arthritis (psoriatic spondyloarthritis, PsSpA), 157 with ankylosing spondylitis (AS) without psoriasis, and 50 matched healthy controls (HC). Serum biomarker concentrations were measured using ELISA. Multivariable regression and receiver operating characteristic analyses were performed.
RESULTS
MMP-3 concentrations were significantly higher and M-CSF significantly lower in each arthritis disease group compared with HC (p ≤ 0.02). MMP-3 concentrations were significantly higher (adjusted odds ratio, OR 1.02 per ng/ml increase in concentration; p = 0.0004) and M-CSF significantly lower (OR 0.44 per ng/ml increase; p = 0.01) in PsA (pPsA and PsSpA combined) compared with PsC. Dkk-1 concentrations were significantly higher (OR 1.22 per ng/mL increase; p = 0.01), and OPG concentrations significantly lower (OR 0.20 per ng/mL increase; p = 0.02) in patients with axial arthritis (PsSpA and AS combined) than in those without (pPsA). Furthermore, Dkk-1 concentrations were significantly higher along a spectrum of increasing axial arthritis; Dkk-1 concentrations were higher in AS compared with PsSpA (OR 1.18 per ng/mL increase; p = 0.02). Receiver operating characteristic analysis showed MMP-3 to be the best single biomarker for differentiating PsA from PsC (AUC 0.70 for a cut-off of 14.51 ng/mL; sensitivity 0.76, specificity 0.60).
CONCLUSIONS
MMP-3 and M-CSF are biomarkers for the presence of arthritis in psoriatic disease, and could therefore be used to screen for PsA in psoriasis cohorts. Dkk-1 and OPG are biomarkers of axial arthritis; they could therefore be used to screen for the presence of axial disease in PsA cases, and help differentiate PsSpA from AS. High concentrations of Dkk-1 in AS and PsSpA compared with HC, support previous reports that Dkk-1 is dysfunctional in the spondyloarthritides.
背景
最近的一项系统评价确定了四个候选血清可溶性骨转换生物标志物（DKK-1、M-CSF、基质金属蛋白酶-3、OPG），它们可能与银屑病关节炎（PsA）相关。我们的目的是：（i）确认并确定这四个生物标志物是否与 PsA 相关；（ii）区分有和无关节炎的银屑病患者；（iii）区分有和无轴性关节炎的 PsA 患者。
方法
一项前瞻性、横断面、双中心研究纳入了 200 例无关节炎的银屑病患者（PsC）、127 例无轴性关节炎的 PsA 患者（pPsA）、117 例有轴性关节炎的 PsA 患者（银屑病性脊柱关节炎，PsSpA）、157 例无银屑病的强直性脊柱炎（AS）患者和 50 例匹配的健康对照者（HC）。采用 ELISA 法检测血清生物标志物浓度。进行多变量回归和受试者工作特征分析。
结果
与 HC 相比，每个关节炎疾病组的 MMP-3 浓度显著升高，M-CSF 浓度显著降低（p≤0.02）。与 PsC 相比，MMP-3 浓度（调整后的优势比，浓度每增加 1ng/ml 增加 1.02；p=0.0004）和 M-CSF 浓度（调整后的优势比，浓度每增加 1ng/ml 降低 0.44；p=0.01）在 PsA（pPsA 和 PsSpA 合并）中显著升高。与无轴性关节炎（pPsA）患者相比，Dkk-1 浓度（每增加 1ng/ml 增加 1.22；p=0.01）和 OPG 浓度（每增加 1ng/ml 降低 0.20；p=0.02）在有轴性关节炎（PsSpA 和 AS 合并）患者中显著升高。此外，Dkk-1 浓度随着轴性关节炎程度的增加而显著升高；与 PsSpA 相比，Dkk-1 浓度在 AS 中更高（每增加 1ng/ml 增加 1.18；p=0.02）。受试者工作特征分析显示，MMP-3 是区分 PsA 与 PsC 的最佳单一生物标志物（截断值为 14.51ng/ml 时，AUC 为 0.70；敏感性 0.76，特异性 0.60）。
结论
MMP-3 和 M-CSF 是银屑病关节炎存在的生物标志物，因此可用于在银屑病患者中筛查 PsA。Dkk-1 和 OPG 是轴性关节炎的生物标志物；因此，它们可用于筛查 PsA 患者中轴性疾病的存在，并有助于区分 PsSpA 与 AS。与 HC 相比，AS 和 PsSpA 中的 Dkk-1 浓度较高，支持先前的报告，即 Dkk-1 在脊柱关节炎中功能失调。
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