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Abstract：
BACKGROUND: Psoriatic arthritis (PsA) is an inflammatory arthritis associated with psoriasis. PsA disease involves flares, which are associated with increased joint inflammation and tissue remodeling. There is a need for identifying biomarkers related to PsA disease activity and flares to improve the management of PsA patients and decrease flares. The tissue turnover imbalance that occurs during the inflammatory and fibro-proliferative processes during flares leads to an increased degradation and/or reorganization of the extracellular matrix (ECM), where increased proteolysis plays a key role. Hence, protease-mediated fragments of inflammatory and tissue-remodeling components could be used as markers reflecting flares in PsA patients.
METHODS: A broad panel of protease-mediated biomarkers reflecting inflammation and tissue remodeling was measured in serum and synovial fluid (SF) obtained from PsA patients experiencing flares (acutely swollen joint[s], PsA-flare). In serum, biomarker levels assessed in PsA-flare patients were compared to controls and in early-diagnosed PsA patients not experiencing flares (referred to as PsA without flare). Furthermore, the biomarker levels assessed in SF from PsA-flare patients were compared to the levels in SF of osteoarthritis (OA) patients.
RESULTS: In serum, levels of the PRO-C3 and C3M, reflecting formation and degradation of the interstitial matrix, were found significantly elevated in PsA-flare compared to controls and PsA without flare. The remodeling marker of the basement membrane, PRO-C4, was significantly elevated in PsA-flare compared to PsA without flare. The inflammation and immune cell activity related markers, CRPM, VICM, and CPa9-HNE were significantly elevated in PsA-flare patients compared to controls and PsA without flare. In addition, VICM (AUC = 0.71), CPa9-HNE (AUC = 0.89), CRPM (AUC = 0.76), and PRO-C3 (AUC = 0.86) showed good discriminatory performance for separating PsA-flare from PsA without flare. In SF, the macrophage activity marker, VICM, was significantly elevated whereas the type II collagen formation marker, PRO-C2, was significantly reduced in the PsA-flare compared to OA. The combination of five serum markers reflecting type III and IV collagen degradation (C3M and C4M, respectively), type III and VI collagen formation (PRO-C3 and PRO-C6, respectively), and neutrophil activity (CPa9-HNE) showed an excellent discriminatory performance (AUC = 0.98) for separating PsA-flare from PsA without flares.
CONCLUSIONS: The serum biomarker panel of C3M, C4M, PRO-C3, PRO-C6, and CPa9-HNE reflecting synovitis, enthesitis, and neutrophil activity may serve as novel tool for quantitatively monitoring flares in PsA patients.
METHODS: A broad panel of protease-mediated biomarkers reflecting inflammation and tissue remodeling was measured in serum and synovial fluid (SF) obtained from PsA patients experiencing flares (acutely swollen joint[s], PsA-flare). In serum, biomarker levels assessed in PsA-flare patients were compared to controls and in early-diagnosed PsA patients not experiencing flares (referred to as PsA without flare). Furthermore, the biomarker levels assessed in SF from PsA-flare patients were compared to the levels in SF of osteoarthritis (OA) patients.
RESULTS: In serum, levels of the PRO-C3 and C3M, reflecting formation and degradation of the interstitial matrix, were found significantly elevated in PsA-flare compared to controls and PsA without flare. The remodeling marker of the basement membrane, PRO-C4, was significantly elevated in PsA-flare compared to PsA without flare. The inflammation and immune cell activity related markers, CRPM, VICM, and CPa9-HNE were significantly elevated in PsA-flare patients compared to controls and PsA without flare. In addition, VICM (AUC = 0.71), CPa9-HNE (AUC = 0.89), CRPM (AUC = 0.76), and PRO-C3 (AUC = 0.86) showed good discriminatory performance for separating PsA-flare from PsA without flare. In SF, the macrophage activity marker, VICM, was significantly elevated whereas the type II collagen formation marker, PRO-C2, was significantly reduced in the PsA-flare compared to OA. The combination of five serum markers reflecting type III and IV collagen degradation (C3M and C4M, respectively), type III and VI collagen formation (PRO-C3 and PRO-C6, respectively), and neutrophil activity (CPa9-HNE) showed an excellent discriminatory performance (AUC = 0.98) for separating PsA-flare from PsA without flares.
CONCLUSIONS: The serum biomarker panel of C3M, C4M, PRO-C3, PRO-C6, and CPa9-HNE reflecting synovitis, enthesitis, and neutrophil activity may serve as novel tool for quantitatively monitoring flares in PsA patients.
摘要：
背景：银屑病关节炎（PsA）是与银屑病相关的炎性关节炎。PsA疾病涉及耀斑，与关节炎症和组织重塑增加有关。需要鉴定与PsA疾病活动性和耀斑相关的生物标志物以改善PsA患者的管理并减少耀斑。在耀斑期间炎症和纤维增殖过程中发生的组织周转失衡导致细胞外基质（ECM）的降解和/或重组增加，其中增加的蛋白水解起关键作用。因此，蛋白酶介导的炎症和组织重塑成分片段可用作反映PsA患者耀斑的标志物。
方法：在从经历耀斑（关节急性肿胀[s]，PsA-耀斑)。在血清中，在PsA-耀斑患者中评估的生物标志物水平与对照组和未经历耀斑的早期诊断的PsA患者(称为无耀斑的PsA)进行比较.此外，比较了PsA-flare患者SF中评估的生物标志物水平与骨关节炎(OA)患者SF中评估的生物标志物水平.
结果：在血清中，PRO-C3和C3M的水平，反映间隙基质的形成和降解，与对照组和无耀斑的PsA相比，PsA耀斑显著升高。基底膜的重塑标记，与没有耀斑的PsA相比,PRO-C4在PsA耀斑中显著升高。炎症和免疫细胞活性相关标志物，CRPM,VICM,与对照组和无耀斑的PsA相比，PsA耀斑患者的CPa9-HNE显着升高。此外,VICM（AUC=0.71），CPa9-HNE（AUC=0.89），CRPM（AUC=0.76），和PRO-C3（AUC=0.86）显示出良好的辨别性能，可将PsA-flare与PsA分离而没有flare。在SF中，巨噬细胞活性标记，VICM,显著升高，而II型胶原形成标志物，与OA相比,PRO-C2在PsA-耀斑中显著降低。反映III型和IV型胶原蛋白降解的五种血清标志物(C3M和C4M，分别)，III型和VI型胶原形成（分别为PRO-C3和PRO-C6），和中性粒细胞活性（CPa9-HNE）显示出优异的辨别性能（AUC=0.98），可将PsA-耀斑与PsA分离而没有耀斑。
结论：C3M的血清生物标志物组，C4M,PRO-C3，PRO-C6和CPa9-HNE反射滑膜炎，附着性炎,和中性粒细胞活性可作为定量监测PsA患者耀斑的新工具。
方法：在从经历耀斑（关节急性肿胀[s]，PsA-耀斑)。在血清中，在PsA-耀斑患者中评估的生物标志物水平与对照组和未经历耀斑的早期诊断的PsA患者(称为无耀斑的PsA)进行比较.此外，比较了PsA-flare患者SF中评估的生物标志物水平与骨关节炎(OA)患者SF中评估的生物标志物水平.
结果：在血清中，PRO-C3和C3M的水平，反映间隙基质的形成和降解，与对照组和无耀斑的PsA相比，PsA耀斑显著升高。基底膜的重塑标记，与没有耀斑的PsA相比,PRO-C4在PsA耀斑中显著升高。炎症和免疫细胞活性相关标志物，CRPM,VICM,与对照组和无耀斑的PsA相比，PsA耀斑患者的CPa9-HNE显着升高。此外,VICM（AUC=0.71），CPa9-HNE（AUC=0.89），CRPM（AUC=0.76），和PRO-C3（AUC=0.86）显示出良好的辨别性能，可将PsA-flare与PsA分离而没有flare。在SF中，巨噬细胞活性标记，VICM,显著升高，而II型胶原形成标志物，与OA相比,PRO-C2在PsA-耀斑中显著降低。反映III型和IV型胶原蛋白降解的五种血清标志物(C3M和C4M，分别)，III型和VI型胶原形成（分别为PRO-C3和PRO-C6），和中性粒细胞活性（CPa9-HNE）显示出优异的辨别性能（AUC=0.98），可将PsA-耀斑与PsA分离而没有耀斑。
结论：C3M的血清生物标志物组，C4M,PRO-C3，PRO-C6和CPa9-HNE反射滑膜炎，附着性炎,和中性粒细胞活性可作为定量监测PsA患者耀斑的新工具。
