Effects of oral prednisolone on biomarkers in synovial tissue and clinical improvement in rheumatoid arthritis
Effects of oral prednisolone on biomarkers in synovial tissue and clinical improvement in rheumatoid arthritis
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DOI：
10.1002/art.20664
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发表时间：
2004-12-01
影响因子：
--
通讯作者：
Tak, PP
中科院分区：
文献类型：
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作者：
Gerlag, DM;Haringman, JJ;Tak, PP
目标。通过使用有效的治疗方法，更好地了解与临床反应相关的滑膜组织参数的变化，从而促进类风湿关节炎（RA）治疗药物的未来研究计划。21名活动性RA患者随机接受口服强的松龙（n = 10）或安慰剂（n = 11）治疗2周。所有患者在治疗前和治疗14天后直接通过关节镜获得滑膜组织活检标本。免疫组化分析细胞浸润和血管分布特征。对染色组织切片进行数字成像分析。采用协方差分析模型进行统计分析。治疗后，接受强的松龙治疗的患者28个关节的平均疾病活动评分（DAS28）比接受安慰剂治疗的患者低2.0个单位（95%可信区间[95% CI] 1.0-3.0）。强的松龙组治疗后平均（+/- sd） DAS28从6.27 +/- 0.95降至4.11 +/- 1.43；安慰剂组的变化最小。对于巨噬细胞，预估强的松龙的作用很大。与接受安慰剂治疗的患者相比，接受积极治疗的患者治疗后巨噬细胞较少（平均628个细胞/毫米(2)[95% CI 328-927]）。在强的松龙组中，CD68+巨噬细胞总数从治疗前的1,038 h 283细胞/mm(2)减少到治疗后的533 +/- 248细胞/mm(2)。积极治疗后，T细胞、浆细胞和成纤维细胞样滑膜细胞的浸润明显减少。我们观察到强的松龙治疗后，α β 3+新生血管和血管生长因子的表达有减少的趋势。泼尼松龙治疗RA与滑膜组织巨噬细胞浸润显著减少相关，提示滑膜巨噬细胞数量可作为临床疗效的生物标志物。
Objective. To create greater understanding of the changes in synovial tissue parameters that occur in conjunction with clinical response by using an effective therapy, in order to facilitate the planning of future studies with therapeutic agents for rheumatoid arthritis (RA).Methods. Twenty-one patients with active RA were randomized to receive either oral prednisolone (n = 10) or placebo (n = 11) for 2 weeks. In all patients, synovial tissue biopsy specimens were obtained by arthroscopy directly before treatment and after 14 days of treatment. Immunohistochemical analysis was performed to characterize the cell infiltrate and vascularity. Stained tissue sections were analyzed by digital imaging. Statistical analysis was performed using an analysis of covariance model.Results. After treatment, the mean Disease Activity Score in 28 joints (DAS28) was 2.0 units lower (95% confidence interval [95% CI] 1.0-3.0) in patients who received prednisolone than in those who received placebo. In the prednisolone group, the mean (+/-SD) DAS28 decreased from 6.27 +/- 0.95 to 4.11 +/- 1.43 after therapy; minimal change was observed in the placebo group. For macrophages, the estimated effect of prednisolone was large. Patients receiving active treatment had fewer (mean 628 cells/mm(2) [95% CI 328-927]) macrophages after therapy compared with those receiving placebo. A reduction in the total number of CD68+ macrophages, from 1,038 h 283 cells/mm(2) before treatment to 533 +/- 248 cells/mm(2) after treatment, was observed in the prednisolone group. There were clear trends toward decreased infiltration by T cells, plasma cells, and fibroblast-like synoviocytes after active treatment. We observed a trend toward a reduction in alphavbeta3+ newly formed blood vessels and expression of vascular growth factors after prednisolone therapy.Conclusion. Prednisolone therapy in RA is associated with a marked reduction in macrophage infiltration in synovial tissue, suggesting that synovial macrophage numbers could be used as a biomarker for clinical efficacy.