TY -的T1 Natalizumab治疗效果持续降低血清水平的纤连蛋白和可溶性粘附分子sVCAM-1和sICAM-3 (P02.114) JF -神经学乔-神经病学SP - P02.114 LP - P02.114六世- 78 - 1补充非盟- Jorg克劳斯盟凯特琳Oppermann AU - Georg Pilz 首页AU -彼得Wipfler盟Shahrzad Afazel AU -伊丽莎白Haschke-Becher盟-尤金Trinka盟-安德里亚勒Y1 - 2012/04/24 UR - //www.ez-admanager.com/content/78/1_Supplement/P02.114.abstract N2 -目的:获得更好的理解潜在的附加效应机制Natalizumab我们分析了短期和长期治疗的影响可溶性粘附分子(sAMs)病人外周血的女士。背景Natalizumab (Tysabri)是一种人性化单克隆抗体用于治疗复发缓和多发性硬化(MS)。它直接绑定到很晚的alpha4-integrin单元激活antigen-4 (VLA-4)和结果检测能力降低疏通alpha 4导致抑制免疫细胞外渗穿过血脑屏障。natalizumab的令人印象深刻的疗效是失色罕见但潜在的严重副作用如渐进多焦点的脑白质病。设计/方法:血清水平的纤连蛋白(FN)和4种不同的地对空导弹(可溶性细胞间粘附molecule-1 2 3 (sICAM-1 2 3)和血管细胞粘附molecule-1 (sVCAM-1))进行了分析前(基线,n = 16), 3个月后(短期,n = 16)和后24个月(长期、n = 14) Natalizumab发作治疗的荧光珠免疫测定和酶联免疫吸附试验。Results: A significant and sustained decrease in serum concentrations of FN, sICAM-3 and sVCAM-1 was observed during the first 3 months (FN p<0.01; sICAM-3 p<0.001; sVCAM-1: p<0.001) and after 24 months (FN p=0.01; sICAM-3 p<0.001; sVCAM-1 p<0.001) of therapy compared to baseline levels. In contrast, serum levels of sICAM-1 and sICAM-2 remained unchanged.Conclusions: The observed decreases in serum levels highlight sICAM-3, sVCAM-1, and FN to be affected by natalizumab therapy. Decreases in sVCAM-1 serum levels have already been previously reported. We add sICAM-3 and the soluble form of the extracellular matrix protein FN. Both, sVCAM-1 and FN have been shown to be directly engaged in VLA-4-mediated extravasation of immune cells and sICAM-3 is important in the initiation of immune responses. Decreased serum levels indicate potential therapy-induced interference with fine-tuning and/or feedback mechanisms between endothelium and immune cells with yet unresolved consequences.Supported by: Biogen-Idec Austria.Disclosure: Dr. Kraus has received personal compensation for activities with Biogen Idec, Bayer Pharmaceuticals Corporation, Sanofi-Aventis Pharmaceuticals, Merck-Serono, Novartis, Genzyme Corporation as a consultant. Dr. Kraus has received research support from Biogen Idec, Bayer Pharmaceuticals Corporation, Sanofi-Aventis Pharmaceuticals, Merck Serono, Novartis, Genzyme Corporation. Dr. Oppermann has nothing to disclose. Dr. Pilz has nothing to disclose. Dr. Wipfler has nothing to disclose. Dr. Afazel has nothing to disclose. Dr. Haschke-Becher has nothing to disclose. Dr. Trinka has received personal compensation for activities with UCB Pharma, Eisai Inc., Sunovion, Medtronic, Pfizer Inc, Ever-Neuropharma and GlaxoSmithKline, Inc. as a consultant and/or speaker. Dr. Trinka has received research support from UCB Pharma, Ever-Neuropharma, Medtronic and GlaxoSmithKline, Inc. Dr. Harrer has nothing to disclose.Tuesday, April 24 2012, 07:30 am-12:00 pm ER -