Synovial Tissue Sublining CD68 Expression Is a Biomarker of Therapeutic Response in Rheumatoid Arthritis Clinical Trials: Consistency Across Centers
Synovial Tissue Sublining CD68 Expression Is a Biomarker of Therapeutic Response in Rheumatoid Arthritis Clinical Trials: Consistency Across Centers
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DOI：
10.3899/jrheum.090348
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发表时间：
2009-08-01
影响因子：
3.9
通讯作者：
Tak, Paul-Peter
中科院分区：
文献类型：
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作者：
Bresnihan, Barry;Pontifex, Eliza;Tak, Paul-Peter
客观的。确定疾病活动的平均变化与滑膜下层 (sl) CD68 表达的平均变化之间的相关性是否可以在不同的学术中心得到证明。方法。选择并编码在利妥昔单抗治疗前和治疗后 160 天的类风湿性关节炎患者的关节镜检查中获得的滑膜活检组织。配对切片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) 来量化亚衬 CD68 表达。结果。对两个不同国家的中心的 CD68sl 表达进行分析后，观察到中心内和中心间的高水平一致性。对于在 AMC 染色的合并切片。 2 位研究人员之间的相关性为 R = 0.942，p = 0.000，对于在 SVUH 染色的切片，R 0.899 p = 0.001。相似地。对于在 AMC 染色的切片，治疗后 Delta CD68sl 表达的中心内相关性为 R = 0998 p = 0.000，对于在 SVUH 染色的切片而言，R = 0.880，p = 0.000。在 AMC 染色的切片的汇总分数的中心间相关性为 R = 0.85，p = 0.000，对于在 SVUH 染色的切片，R = 0.62，p = 0.001。不同研究中 Delta DAS（疾病活动评分）和 Delta CD68sl 表达之间的一致相关性得到证实（Pearson 相关性 = 0.895，p < 0.001）。根据 AMC 和 SVUH 的分析计算得出的 Delta CD68sl 标准化响应平均值始终为 0.5 或更高，表明检测变化的潜力为中等到高。结论。平均 Delta DAS 和平均 Delta CD68sl 表达之间的相关性在 2 个中心得到证实。连续活检样本的检查可以可靠地用于在药物开发的早期阶段筛选炎症部位有趣的生物效应。 （风湿杂志 2009；36：1800-2；doi：10.3899/jrheum.090348）
Objective. 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.Methods. 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.Results. After analysis of CD68sl expression at centers in 2 different countries, high levels of intra- center 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 Delta CD68sl expression after treatment were R = 0998 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 con-elation between Delta DAS (Disease Activity Score) and Delta CD68sl expression across different studies (Pearson correlation = 0.895, p < 0.001) was confirmed. The standardized response mean values for Delta CD68sl, calculated from analyses at both AMC and SVUH, were consistently 0.5 or greater, indicating a moderate to high potential to detect change.Conclusion. The correlation between mean Delta DAS and mean Delta CD68sl 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. (J Rheumatol 2009;36:1800-2; doi: 10.3899/jrheum.090348)