Neo-Epitopes--Fragments of Cartilage and Connective Tissue Degradation in Early Rheumatoid Arthritis and Unclassified Arthritis.
Neo-Epitopes--Fragments of Cartilage and Connective Tissue Degradation in Early Rheumatoid Arthritis and Unclassified Arthritis.
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DOI：
10.1371/journal.pone.0149329
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Bay-Jensen AC
中科院分区：
文献类型：
--
作者：
Maijer KI;Gudmann NS;Karsdal MA;Gerlag DM;Tak PP;Bay-Jensen AC
类风湿性关节炎（RA）的组织破坏主要由基质金属蛋白酶（MMP）介导，从而产生蛋白质片段。以前的研究表明，这些片段包括MMP介导的I型、II型和III型胶原降解，瓜氨酸化和MMP降解的波形蛋白和MMP降解的C反应蛋白。我们评估了测量上述片段的特定序列的血清水平的生物标志物是否会提供早期关节炎的诊断和/或预后过程的进一步信息。招募了92名早期关节炎患者（关节炎持续时间<1年，DMARD初治）。患者符合ACR/EULAR 2010 RA标准（n = 60）或患有未分类关节炎（UA）（n = 32）。2年随访后符合RA标准的患者分为非糜烂性（n = 25）或糜烂性疾病（n = 13）。在基线血清中测量生物标志物：C1 M、C2M、C3 M、VICM和CRPM的浓度。C1 M、C3 M和CRPM能够区分92例患者的UA和RA基线诊断，AUROC分别为0.64（95%CI 0.517至0.762）、0.73（95%CI 0.622至0.838）和0.68（95%CI 0.570至0.795）。C2M在38例患者中显示出区分非糜烂性和糜烂性疾病的潜力，AUROC为0.75（95%CI 0.597至0.910）。所有应用的生物标志物与一个或多个疾病活动参数相关：DAS 28、ESR、CRP、SJC 66、TJC 68和/或HAQ。这是第一项评估关节炎早期应用生物标志物的研究。C1 M、C3 M、CRPM可能是早期RA患者最佳的诊断指标，而C2M水平高则表明早期RA患者在随访时疾病进展。
Tissue destruction in rheumatoid arthritis (RA) is predominantly mediated by matrix metalloproteinases (MMPs), thereby generating protein fragments. Previous studies have revealed that these fragments include MMP-mediated collagen type I, II, and III degradation, citrullinated and MMP-degraded vimentin and MMP degraded C-reactive protein. We evaluated if biomarkers measuring serum levels of specific sequences of the mentioned fragments would provide further information of diagnostic and/or prognostic processes in early arthritis. Ninety-two early arthritis patients (arthritis duration<1 year, DMARD naïve) were enrolled. Patients either fulfilled the ACR/EULAR2010 criteria for RA (n = 60) or had unclassified arthritis (UA) (n = 32). Patients fulfilling the RA criteria after 2 years follow-up were classified into non-erosive (n = 25), or erosive disease (n = 13). Concentrations of the biomarkers: C1M, C2M, C3M, VICM and CRPM were measured in baseline serum. C1M, C3M and CRPM were able to discriminate between the UA and RA baseline diagnosis in 92 patients with an AUROC of 0.64 (95%CI 0.517 to 0.762), 0.73 (95%CI 0.622 to 0.838) and 0.68 (95%CI 0.570 to 0.795). C2M showed a potential for discrimination between non-erosive and erosive disease in 38 patients with an AUROC of 0.75 (95%CI 0.597 to 0.910). All of the applied biomarkers correlated with one or more of the disease activity parameters: DAS28, ESR, CRP, SJC66, TJC68 and/or HAQ. This is the first study evaluating the applied biomarkers at this early stage of arthritis. C1M, C3M, CRPM might be the best diagnostic marker, whereas high levels of C2M indicated progression of disease at follow-up in early RA patients.