Bresnihan Barry, Pontifex Eliza, Thurlings Rogier M, Vinkenoog Marjolein, El-Gabalawy Hani, Fearon Ursula, Fitzgerald Oliver, Gerlag Danielle M, Rooney Terence, van de Sande Marleen G, Veale Douglas, Vos Koen, Tak Paul-Peter
St. Vincent's University Hospital, Dublin, Ireland.
J Rheumatol. 2009 Aug;36(8):1800-2. doi: 10.3899/jrheum.090348.
To determine whether the correlation between the mean change in disease activity and the mean change in synovial sublining (sl) CD68 expression could be demonstrated across different academic centers.
Synovial biopsies obtained at arthroscopy from patients with rheumatoid arthritis before and 160 days after rituximab therapy were selected and coded. Paired sections were processed independently at Amsterdam Medical Center (AMC) and at St. Vincent's University Hospital (SVUH), Dublin. Digital image analysis (DIA) was employed at both centers to quantify sublining CD68 expression.
After analysis of CD68sl expression at centers in 2 different countries, high levels of intracenter and intercenter agreement were observed. For the pooled sections stained at AMC, the correlation between 2 investigators was R = 0.942, p = 0.000, and for sections stained at SVUH, R = 0.899, p = 0.001. Similarly, the intracenter correlations for DeltaCD68sl expression after treatment were R = 0.998, p = 0.000, for sections stained at AMC and R = 0.880, p = 0.000, for sections stained at SVUH. The intercenter correlation for the pooled scores of sections stained at AMC was R = 0.85, p = 0.000, and for the sections stained at SVUH, R = 0.62, p = 0.001. The consistent correlation between DeltaDAS (Disease Activity Score) and DeltaCD68sl expression across different studies (Pearson correlation = 0.895, p < 0.001) was confirmed. The standardized response mean values for DeltaCD68sl, calculated from analyses at both AMC and SVUH, were consistently 0.5 or greater, indicating a moderate to high potential to detect change.
The correlation between mean DeltaDAS and mean DeltaCD68sl expression was confirmed across 2 centers. Examination of serial biopsy samples can be used reliably to screen for interesting biological effects at the site of inflammation at an early stage of drug development.
确定在不同学术中心之间是否能够证明疾病活动度的平均变化与滑膜衬里（sl）CD68表达的平均变化之间存在相关性。
选取类风湿关节炎患者在接受利妥昔单抗治疗前及治疗160天后关节镜检查时获取的滑膜活检组织并进行编码。配对切片分别在阿姆斯特丹医学中心（AMC）和都柏林圣文森特大学医院（SVUH）独立处理。两个中心均采用数字图像分析（DIA）对衬里CD68表达进行定量分析。
对来自2个不同国家中心的CD68sl表达进行分析后，观察到中心内和中心间的高度一致性。对于在AMC染色的汇总切片，2名研究者之间的相关性为R = 0.942，p = 0.000；对于在SVUH染色的切片，R = 0.899，p = 0.001。同样，治疗后DeltaCD68sl表达的中心内相关性，在AMC染色的切片中为R = 0.998，p = 0.000，在SVUH染色的切片中为R = 0.880，p = 0.000。在AMC染色的切片汇总评分的中心间相关性为R = 0.85，p = 0.000，在SVUH染色的切片中为R = 0.62，p = 0.001。不同研究中DeltaDAS（疾病活动评分）与DeltaCD68sl表达之间一致的相关性（Pearson相关性 = 0.895，p < 0.001）得到了证实。根据AMC和SVUH的分析计算得出的DeltaCD68sl标准化反应均值始终为0.5或更高，表明具有中等至高的检测变化潜力。
在2个中心之间证实了平均DeltaDAS与平均DeltaCD68sl表达之间的相关性。在药物开发的早期阶段，对连续活检样本的检查可可靠地用于筛查炎症部位有趣的生物学效应。
