Andersen Martin, Boesen Mikael, Ellegaard Karen, Christensen Robin, Söderström Kalle, Søe Niels, Spee Pieter, Mørch Ulrik Gw, Torp-Pedersen Søren, Bartels Else Marie, Danneskiold-Samsøe Bente, Vendel Nina, Karlsson Lars, Bliddal Henning
Arthritis Res Ther. 2014 May 5;16(3):R107. doi: 10.1186/ar4557.
Despite the widespread use of magnetic resonance imaging (MRI) and Doppler ultrasound for the detection of rheumatoid arthritis (RA) disease activity, little is known regarding the association of imaging-detected activity and synovial pathology. The purpose of this study was to compare site-specific release of inflammatory mediators and evaluate the corresponding anatomical sites by examining colour Doppler ultrasound (CDUS) and MRI scans.
RA patients were evaluated on the basis of CDUS and 3-T MRI scans and subsequently underwent synovectomy using a needle arthroscopic procedure of the hand joints. The synovial tissue specimens were incubated for 72 hours, and spontaneous release of monocyte chemoattractant protein 1 (MCP-1), interleukin 6 (IL-6), macrophage inflammatory protein 1β (MIP-1β) and IL-8 was measured by performing multiplex immunoassays. Bone marrow oedema (BME), synovitis and erosion scores were estimated on the basis of the rheumatoid arthritis magnetic resonance imaging score (RAMRIS). Mixed models were used for the statistical analyses. Parsimony was achieved by omitting covariates with P > 0.1 from the statistical model.
Tissue samples from 58 synovial sites were obtained from 25 patients. MCP-1 was associated with CDUS activity (P = 0.009, approximate Spearman's ρ = 0.41), RAMRIS BME score (P = 0.01, approximate Spearman's ρ = 0.42) and RAMRIS erosion score (P = 0.03, approximate Spearman's ρ = 0.31). IL-6 was associated with RAMRIS synovitis score (P = 0.04, approximate Spearman's ρ = 0.50), BME score (P = 0.04, approximate Spearman's ρ = 0.31) and RAMRIS erosion score (P = 0.03, approximate Spearman's ρ = 0.35). MIP-1β was associated with CDUS activity (P = 0.02, approximate Spearman's ρ = 0.38) and RAMRIS synovitis scores (P = 0.02, approximate Spearman's ρ = 0.63). IL-8 associations with imaging outcome measures did not reach statistical significance.
The association between imaging activity and synovial inflammatory mediators underscores the high sensitivity of CDUS and MRI in the evaluation of RA disease activity. The associations found in our present study have different implications for synovial mediator releases and corresponding imaging signs. For example, MCP-1 and IL-6 were associated with both general inflammation and bone destruction, in contrast to MIP-1β, which was involved solely in general synovitis. The lack of association of IL-8 with synovitis was likely underestimated because of a large proportion of samples above assay detection limits among the patients with the highest synovitis scores.
尽管磁共振成像（MRI）和多普勒超声在类风湿关节炎（RA）疾病活动检测中广泛应用，但关于成像检测到的活动与滑膜病理学之间的关联却知之甚少。本研究的目的是通过检查彩色多普勒超声（CDUS）和MRI扫描，比较炎症介质的部位特异性释放，并评估相应的解剖部位。
对RA患者进行CDUS和3-T MRI扫描评估，随后采用手部关节针式关节镜手术进行滑膜切除术。将滑膜组织标本孵育72小时，通过多重免疫测定法测量单核细胞趋化蛋白1（MCP-1）、白细胞介素6（IL-6）、巨噬细胞炎性蛋白1β（MIP-1β）和IL-8的自发释放。根据类风湿关节炎磁共振成像评分（RAMRIS）评估骨髓水肿（BME）、滑膜炎和侵蚀评分。采用混合模型进行统计分析。通过从统计模型中省略P>0.1的协变量来实现简约性。
从25例患者中获取了58个滑膜部位的组织样本。MCP-1与CDUS活动相关（P=0.009，近似Spearman's ρ=0.41）、RAMRIS BME评分相关（P=0.01，近似Spearman's ρ=0.42）以及RAMRIS侵蚀评分相关（P=0.03，近似Spearman's ρ=0.31）。IL-6与RAMRIS滑膜炎评分相关（P=0.04，近似Spearman's ρ=0.50）、BME评分相关（P=0.04，近似Spearman's ρ=0.31）以及RAMRIS侵蚀评分相关（P=0.03，近似Spearman's ρ=0.35）。MIP-1β与CDUS活动相关（P=0.02，近似Spearman's ρ=0.38）以及RAMRIS滑膜炎评分相关（P=0.02，近似Spearman's ρ=0.63）。IL-8与成像结果指标之间的关联未达到统计学显著性。
成像活动与滑膜炎症介质之间的关联强调了CDUS和MRI在评估RA疾病活动中的高敏感性。我们在本研究中发现的关联对滑膜介质释放和相应的成像征象具有不同的意义。例如，与仅参与一般滑膜炎的MIP-1β相反，MCP-1和IL-6与一般炎症和骨破坏均相关。IL-8与滑膜炎缺乏关联可能是由于在滑膜炎评分最高的患者中，很大一部分样本高于检测限而被低估。
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