Decrease in cellularity and expression of adhesion molecules by anti-tumor necrosis factor alpha monoclonal antibody treatment in patients with rheumatoid arthritis
Decrease in cellularity and expression of adhesion molecules by anti-tumor necrosis factor alpha monoclonal antibody treatment in patients with rheumatoid arthritis
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DOI：
10.1002/art.1780390702
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发表时间：
1996-07-01
影响因子：
--
通讯作者：
Maini, RN
中科院分区：
文献类型：
--
作者：
Tak, PP;Taylor, PC;Maini, RN
Objective.研究了嵌合抗肿瘤坏死因子α（TNF α）单克隆抗体（MAb）治疗对滑膜炎症的影响，以阐明抗TNF α治疗导致滑膜组织（ST）中粘附分子下调和炎性细胞流入减少的假设。本文对14例类风湿关节炎（RA）患者进行了抗肿瘤坏死因子α单抗（cA 2）治疗前及治疗后4周滑膜活检标本的免疫组织化学研究。RA患者经10 mg/kg或20 mg/kg cA 2治疗后，T细胞和粘附分子（血管细胞粘附分子1和E-选择素）的平均评分均显著降低（P < 0.03）。cA 2给药后粘附分子表达减少和类风湿性ST细胞结构减少支持以下假设：抗TNF α治疗的抗肿瘤作用可能部分由ST中精氨酸诱导的血管粘附分子下调，从而减少细胞进入关节。
Objective. The effect of chimeric anti-tumor necrosis factor alpha (TNF alpha) monoclonal antibody (MAb) therapy on synovial inflammation was studied in order to address the hypothesis that anti-TNF alpha therapy leads to down-regulation of adhesion molecules and a decrease in inflammatory cell influx in synovial tissue (ST).Methods. The immunohistologic features of synovial biopsy specimens, both before and 4 weeks after anti-TNF alpha MAb (cA2) therapy, were studied in 14 patients with rheumatoid arthritis (RA), The patients either received a placebo (n = 2), or were given intravenous doses of cA2 at 10 mg/kg (n = 5) or 20 mg/kg (n = 7).Results. A significant (P < 0.03) reduction in the mean scores for T cells and for the adhesion molecules, vascular cell adhesion molecule 1 and E-selectin, was observed after therapy with 10 mg/kg or 20 mg/kg of cA2 in RA patients.Conclusion. The reduced expression of adhesion molecules, and the decrease in cellularity of rheumatoid ST after cA2 administration support the hypothesis that the antiinflammatory effect of anti-TNF alpha therapy might be partly explained by down-regulation of cytokine-inducible vascular adhesion molecules in ST, with a consequent reduction of cell traffic into joints.