Natalizumab effects on immune cell responses in multiple sclerosis
Natalizumab effects on immune cell responses in multiple sclerosis
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DOI：
10.1002/ana.20859
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发表时间：
2006-05-01
影响因子：
11.2
通讯作者：
Bar-Or, A
中科院分区：
文献类型：
--
作者：
Niino, M;Bodner, C;Bar-Or, A
目的：我们的目的是研究natalizumab对多发性硬化症（MS）患者免疫细胞表型和功能的体内生物学效应。方法：连续每月输注natalizumab前后取血，追踪免疫细胞VLA-4的功能表达及迁移能力。评估输注对免疫细胞激活阈值的影响。结果：注射前不同免疫细胞亚群的hla -4表达不同。Natalizumab显著地（尽管部分地）降低了循环免疫细胞上的vla4表达。细胞亚群受到不同程度的影响。治疗显著降低了免疫细胞的迁移能力，这与vla4表达的变化密切相关。单次剂量的影响不饱和，也不会在每个月的剂量间隔中持续存在。输液效果因患者而异，但在个体患者中，多次输液效果非常稳定。治疗显著调节了免疫细胞的增殖反应。解释：据我们所知，我们提供了natalizumab降低免疫细胞迁移能力的第一个概念证明。我们的前瞻性研究进一步表明，治疗的效果可能(1)对不同的免疫细胞亚群不同，(2)不能在当前剂量间隔内持续，(3)在个体患者中具有独特的特征，(4)包括免疫细胞激活阈值的调节。监测这些参数可能与正在进行的安全性和有效性考虑相关。
Objective: Our objective was to study in vivo biological effects of natalizumab on immune cell phenotype and function in multiple sclerosis (MS) patients.Methods: Blood was obtained before and after serial monthly natalizumab infusions to track functional expression of VLA-4 and migratory capacity of immune cells. The impact of infusion on activation thresholds of immune cells was evaluated.Results: Preinfusion VLA-4 expression differed across immune cell subsets. Natalizumab significantly, albeit partially, diminished VLA-4 expression on circulating immune cells. Cell subsets were differentially affected. Treatment significantly decreased migratory capacity of immune cells, correlating well with changes in VLA-4 expression. Effects of a single dose were not saturating and did not persist through the monthly dose interval. Infusion effect varied across patients but was remarkably stable in individual patients, over multiple infusions. Treatment significantly modulated proliferative responses of immune cells.Interpretation: To our knowledge, we provide first proof of concept that natalizumab diminishes migratory capacity of immune cells. Our prospective study further shows that effects of therapy likely (1) differ for distinct immune cell subsets, (2) are not sustained over current dose interval, (3) have unique profiles in individual patients, and (4) include modulation of activation threshold of immune cells. Monitoring these parameters could be relevant to ongoing safety and efficacy considerations.