Brain Center Rudolf Magnus, Department of Neurology and Neurosurgery, University Medical Center Utrecht, Utrecht, The Netherlands.
J Neurol Neurosurg Psychiatry. 2014 Oct;85(10):1145-8. doi: 10.1136/jnnp-2013-306227. Epub 2013 Dec 11.
Multifocal motor neuropathy (MMN) is often responsive to treatment with intravenous immunoglobulin (IVIg), but the optimal dose and intervals of IVIg maintenance treatment have not been established. Increase in IgG concentration (ΔIgG) after IVIg infusion has recently been identified as determinant of outcome in Guillain-Barré syndrome. ΔIgG may therefore represent a potentially useful biomarker to optimise IVIg dosing in patients with MMN.
The aims of this study were to determine variability of IVIg pharmacokinetics in patients with MMN in relation to treatment response, and to establish whether interindividual differences in IVIg pharmacokinetics were associated with genetic polymorphisms of the endothelial IgG receptor (FcRn) which determines IgG half-life.
Twenty-three patients with MMN receiving their first IVIg treatment at a cumulative dose of 2.0 g/kg in 5 days were included. A good treatment response was defined as an increase in muscle strength of at least one Medical Research Council point in minimally two muscle groups. IgG concentrations in serum were determined at baseline, at day 1 and day 5 of the IVIg course, and 3 weeks after treatment. FcRn copy number variation and differences in repeat length of the variable number of tandem repeats in the FcRn gene were determined by quantitative PCR and Sanger sequencing.
Seventeen patients (74%) had a good response to treatment. Total IgG and ΔIgG levels showed large variation between patients. Mean ΔIgG was higher in IVIg responders than in non-responders, with the largest difference on day 1 (11.1 g/L vs 4.5 g/L, p=0.06), but our study lacked power to show statistically significant differences. Genetic variation in the FcRn gene was not associated with ΔIgG levels or response to treatment.
IVIg pharmacokinetics varies in patients with MMN and may be associated with clinical response.
多灶性运动神经病（MMN）常对静脉注射免疫球蛋白（IVIg）治疗有反应，但 IVIg 维持治疗的最佳剂量和间隔尚未确定。最近发现，IVIg 输注后 IgG 浓度的增加（ΔIgG）是吉兰-巴雷综合征结局的决定因素。因此，ΔIgG 可能代表一种优化 MMN 患者 IVIg 剂量的潜在有用生物标志物。
本研究旨在确定 MMN 患者 IVIg 药代动力学的变异性与治疗反应的关系，并确定 IVIg 药代动力学的个体间差异是否与决定 IgG 半衰期的内皮 IgG 受体（FcRn）的遗传多态性有关。
纳入 23 例接受首次 2.0 g/kg 累积剂量 IVIg 治疗的 MMN 患者，共 5 天。治疗反应良好定义为至少有两个肌肉群的肌力至少增加一个医学研究委员会（MRC）点。在 IVIg 疗程的基线、第 1 天和第 5 天以及治疗后 3 周，测定血清 IgG 浓度。通过定量 PCR 和 Sanger 测序确定 FcRn 拷贝数变异和 FcRn 基因中可变数串联重复的重复长度差异。
17 例（74%）患者对治疗有良好反应。患者之间总 IgG 和 ΔIgG 水平差异较大。IVIg 反应者的平均 ΔIgG 高于非反应者，第 1 天的差异最大（11.1 g/L 比 4.5 g/L，p=0.06），但本研究缺乏统计学显著差异的效力。FcRn 基因的遗传变异与 ΔIgG 水平或治疗反应无关。
MMN 患者的 IVIg 药代动力学存在差异，可能与临床反应相关。
