Gudmann Natasja Stæhr, Munk Heidi Lausten, Christensen Anne Friesgaard, Ejstrup Leif, Sørensen Grith Lykke, Loft Anne Gitte, Karsdal Morten Asser, Bay-Jensen Anne-Christine, He Yi, Siebuhr Anne Sofie, Junker Peter
Nordic Bioscience Biomarkers and Research, Herlev Hovedgade 207, Herlev, 2730, Denmark.
Department of Rheumatology, Odense University Hospital, Odense, Denmark.
Arthritis Res Ther. 2016 Jun 16;18(1):141. doi: 10.1186/s13075-016-1040-z.
Psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) are chronic inflammatory rheumatic diseases with complex origins. Both are characterized by altered extracellular matrix remodeling in joints and entheses that results in destructive and osteochondral proliferative lesions. There is a need for biomarkers reflecting core disease pathways for diagnosis and disease mapping. Pro-C2 reflects mature cartilage collagen type IIB formation, while C-Col10 represents turnover of type X collagen, which is exclusively expressed by hypertrophic chondrocytes. The objectives of this study were to study cartilage metabolism in axSpA and PsA by assessing Pro-C2 and C-Col10 and to evaluate their diagnostic utility against a healthy reference population.
Patients with PsA (n = 101) or axSpA (n = 110) were recruited consecutively from three rheumatology outpatient clinics. Demographic and clinical disease measures were recorded. Pro-C2 and C-Col10 were quantified in serum by using newly developed and specific competitive enzyme-linked immunosorbent assays based on monoclonal antibodies. One-way analysis of variance and Tukey's multiple comparison tests were performed on log-transformed data. ROC curve analysis was carried out to evaluate their discriminative power.
Pro-C2 levels in serum were significantly increased in both axSpA (median concentration 1.11 ng/ml, 0.67-1.64) and PsA (median concentration 1.03 ng/ml, 0.53-1.47) compared with healthy controls (median concentration 0.30 ng/ml, 0.16-0.41) (p < 0.0001). Pro-C2 did not differ according to treatment. C-Col10 was slightly but equally elevated in the PsA and axSpA groups vs. the control group, but it was significantly lower in patients with axSpA undergoing tumor necrosis factor-α inhibitor (TNFi) treatment. ROC curve analysis revealed AUCs of 0.85 (95 % CI 0.79-0.89) for axSpA and 0.81 (95 % CI 0.75-0.86) for PsA.
These findings indicate that cartilage collagen metabolism was enhanced in the axSpA and PsA groups compared with the healthy control group. The lower C-Col10 level in patients with axSpA undergoing TNFi treatment may reflect that hypertrophic chondrocytes in axSpA are targeted by TNFi. ROC curve analysis showed a diagnostic potential for Pro-C2 in axSpA and PsA.
银屑病关节炎(PsA)和轴性脊柱关节炎(axSpA)是起源复杂的慢性炎症性风湿性疾病。两者的特征均为关节和附着点处细胞外基质重塑改变,导致破坏性和骨软骨增生性病变。需要反映核心疾病途径的生物标志物用于诊断和疾病图谱绘制。前C2反映成熟的IIB型软骨胶原蛋白的形成,而C - 骨胶原X代表X型胶原蛋白的周转,其仅由肥大软骨细胞表达。本研究的目的是通过评估前C2和C - 骨胶原X来研究axSpA和PsA中的软骨代谢,并评估它们相对于健康对照人群的诊断效用。
从三个风湿病门诊连续招募PsA患者(n = 101)或axSpA患者(n = 110)。记录人口统计学和临床疾病指标。使用基于单克隆抗体新开发的特异性竞争酶联免疫吸附测定法对血清中的前C2和C - 骨胶原X进行定量。对对数转换后的数据进行单因素方差分析和Tukey多重比较检验。进行ROC曲线分析以评估它们的鉴别能力。
与健康对照(中位浓度0.30 ng/ml,0.16 - 0.41)相比,axSpA(中位浓度1.11 ng/ml,0.67 - 1.64)和PsA(中位浓度1.03 ng/ml,0.53 - 1.47)患者血清中的前C2水平均显著升高(p < 0.0001)。前C2水平不受治疗影响。与对照组相比,PsA组和axSpA组的C - 骨胶原X略有升高但程度相同,但接受肿瘤坏死因子-α抑制剂(TNFi)治疗的axSpA患者中的C - 骨胶原X显著降低。ROC曲线分析显示axSpA的AUC为0.85(95%CI 0.79 - 0.89),PsA的AUC为0.81(95%CI 0.75 - 0.86)。
这些发现表明,与健康对照组相比,axSpA组和PsA组的软骨胶原代谢增强。接受TNFi治疗的axSpA患者中较低的C - 骨胶原X水平可能反映出axSpA中的肥大软骨细胞是TNFi的作用靶点。ROC曲线分析显示前C2在axSpA和PsA中具有诊断潜力。