Synovial tissue response to rituximab: mechanism of action and identification of biomarkers of response.
Synovial tissue response to rituximab: mechanism of action and identification of biomarkers of response.
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滑膜组织对利妥昔单抗的反应：作用机理和反应生物标志物的鉴定。
DOI：
10.1136/ard.2007.080960
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发表时间：
2008-07
影响因子：
27.4
通讯作者：
Tak, P. P.
中科院分区：
文献类型：
--
作者：
Thurlings, R. M.;Vos, K.;Wijbrandts, C. A.;Zwinderman, A. H.;Gerlag, D. M.;Tak, P. P.
研究利妥昔单抗治疗类风湿关节炎（RA）患者的滑膜组织，并确定可能的临床反应预测因子。共有24例RA患者在开始利妥昔单抗治疗前、治疗后4周和16周接受了滑膜活检（未在输注皮质类固醇以防止偏倚）。进行免疫组织化学分析，并通过数字图像分析对染色切片进行分析。线性回归分析用于确定临床反应的预测因子。28关节疾病活动评分（DAS 28）在4周时没有改变，但在16周和24周时显著降低。血清IgM类风湿因子（RF）水平在24周时显著降低，抗瓜氨酸肽抗体（ACPA）水平在36周时显著降低。外周血B细胞在4周时耗尽，并在24周时开始恢复。滑膜B细胞在4周时显著减少，但并非所有患者都完全耗尽;一些患者在16周时进一步减少。我们发现巨噬细胞在4周时显著减少，在16周时更明显。在该时间点，T细胞也显著减少。浆细胞的减少预测了24周时的临床改善。结果支持B细胞协调局部细胞浸润的观点。临床应答者的血清学和组织应答的动力学与利妥昔单抗部分通过对与自身抗体产生相关的浆细胞的间接作用发挥作用的观点一致，这有助于解释利妥昔单抗治疗后的延迟应答。试验注册号：ISRCTN 05568900。
To investigate the synovial tissue in patients with rheumatoid arthritis (RA) treated with rituximab and to identify possible predictors of clinical response. A total of 24 patients with RA underwent synovial biopsy before, 4 and 16 weeks after initiation of rituximab treatment (without peri-infusional corticosteroids to prevent bias). Immunohistochemical analysis was performed and stained sections were analysed by digital image analysis. Linear regression analysis was used to identify predictors of clinical response. The 28-joint Disease Activity Score (DAS28) was unaltered at 4 weeks, but significantly reduced at 16 and 24 weeks. Serum levels of IgM-rheumatoid factor (RF) decreased significantly at 24 weeks and anti-citrullinated peptide antibody (ACPA) levels at 36 weeks. Peripheral blood B cells were depleted at 4 weeks and started to return at 24 weeks. Synovial B cells were significantly decreased at 4 weeks, but were not completely depleted in all patients; there was a further reduction at 16 weeks in some patients. We found a significant decrease in macrophages at 4 weeks, which was more pronounced at 16 weeks. At that timepoint, T cells were also significantly decreased. The reduction of plasma cells predicted clinical improvement at 24 weeks. The results support the view that B cells orchestrate local cellular infiltration. The kinetics of the serological as well as the tissue response in clinical responders are consistent with the notion that rituximab exerts its effects in part by an indirect effect on plasma cells associated with autoantibody production, which could help explain the delayed response after rituximab treatment. Trial registration number: ISRCTN05568900.
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影响因子：
4.9
作者：
Haringman JJ;Vinkenoog M;Gerlag DM;Smeets TJ;Zwinderman AH;Tak PP
通讯作者：
Tak PP
影响因子：
--
作者：
Emery, P;Fleischmann, R;Shaw, TM
通讯作者：
Shaw, TM
影响因子：
--
作者：
Gerlag, DM;Haringman, JJ;Tak, PP
通讯作者：
Tak, PP
影响因子：
158.5
作者：
Edwards, JCW;Szczepanski, L;Shaw, T
通讯作者：
Shaw, T
影响因子：
--
作者：
Cohen, Stanley B.;Emery, Paul;Totoritis, Mark C.
通讯作者：
Totoritis, Mark C.