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. 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. 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. 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.

中文翻译：

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研究蛋白酶介导的炎症和组织重塑肽作为与银屑病关节炎发作相关的生物标志物


银屑病关节炎（PsA）是一种与银屑病相关的炎症性关节炎。银屑病关节炎疾病涉及耀斑，这与关节炎症和组织重塑的增加有关。需要鉴定与 PsA 疾病活动和发作相关的生物标志物，以改善 PsA 患者的管理并减少发作。发作期间炎症和纤维增殖过程中发生的组织周转不平衡导致细胞外基质（ECM）降解和/或重组增加，其中蛋白水解作用的增加起着关键作用。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 患者病情发作的标记物。在从经历耀斑（关节急性肿胀、银屑病关节炎耀斑）的 PsA 患者获得的血清和滑液 (SF) 中测量了一系列反映炎症和组织重塑的蛋白酶介导的生物标志物。在血清中，将 PsA 发作患者中评估的生物标志物水平与对照以及未经历发作的早期诊断 PsA 患者（称为无发作的 PsA）进行比较。此外，将 PsA 发作患者 SF 中评估的生物标志物水平与骨关节炎 (OA) 患者 SF 中的水平进行比较。在血清中，与对照组和无耀斑的 PsA 相比，PsA 耀斑患者的 PRO-C3 和 C3M 水平（反映间质基质的形成和降解）显着升高。与无耀斑的 PsA 相比，银屑病耀斑患者的基底膜重塑标记物 PRO-C4 显着升高。与对照组和无发作的 PsA 相比，PsA 发作患者的炎症和免疫细胞活性相关标记物 CRPM、VICM 和 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）在区分PsA耀斑和无耀斑的PsA方面表现出良好的区分性能。与 OA 相比，在 SF 中，巨噬细胞活性标记物 VICM 显着升高，而 II 型胶原形成标记物 PRO-C2 在 PsA 耀斑中显着降低。反映 III 型和 IV 型胶原降解（分别为 C3M 和 C4M）、III 型和 VI 型胶原形成（分别为 PRO-C3 和 PRO-C6）以及中性粒细胞活性（CPa9-HNE）的五种血清标志物的组合显示出极好的结果。将 PsA 耀斑与无耀斑的 PsA 分开的区分性能（AUC = 0.98）。反映滑膜炎、附着点炎和中性粒细胞活性的 C3M、C4M、PRO-C3、PRO-C6 和 CPa9-HNE 血清生物标志物组可作为定量监测 PsA 患者耀斑的新工具。