The role of IVIg in the treatment of patients with stiff person syndrome and other neurological diseases associated with anti-GAD antibodies
The role of IVIg in the treatment of patients with stiff person syndrome and other neurological diseases associated with anti-GAD antibodies
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DOI：
10.1007/s00415-005-1105-4
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发表时间：
2005-05-01
影响因子：
6
通讯作者：
Dalakas, MC
中科院分区：
文献类型：
--
作者：
Dalakas, MC
引言高滴度抗GAD抗体的特点是在僵硬人综合征（SPS）患者。其他CNS疾病，很少与高抗GAD抗体滴度相关，包括：a）SPS+，一种以SPS和小脑共济失调为特征的综合征; B）Batten病;和c）罕见的癫痫和特发性小脑共济失调患者。目前，高滴度抗GAD抗体仅作为CNS内自身免疫过程的标志物，因为它们在上述疾病中的致病作用尚未确定。在SPS中，有证据表明自身免疫发病机制基于：疾病与其他自身免疫性疾病或自身抗体的相关性;免疫遗传学背景; CSF中存在寡克隆IgG条带，鞘内抗GAD抗体合成增加和对免疫治疗的反应。SPS是唯一的GAD阳性的中枢神经系统疾病的免疫治疗的对照研究已经carried.Methods 16个抗GAD抗体阳性患者随机接受IVIg或安慰剂3个月。在一次冲洗后，他们又进行了三个月的替代疗法。疗效基于僵硬指数和敏感性增强（痉挛）从基线至输注第2个月和第3个月的分布评分差异。直接治疗和结转效果进行了比较，为两组。结果在IVIg随机化患者的僵硬评分显着下降，从第1个月至4，但反弹时，他们交叉安慰剂。相比之下，安慰剂随机组的评分在第1-4个月保持不变，但在交叉至IVIg后显著下降。11名接受IVIg的患者能够独立行走，停止跌倒并承担家庭或工作职责。补助的期限从6至12周不等，最长可达一年。IVIg治疗后抗GAD（65）抗体滴度下降，而安慰剂治疗后抗GAD（65）抗体滴度无明显下降。结论IVIg治疗对其他药物无效的SPS是一种安全有效的治疗方法。IVIg是否对其他GAD阳性的神经系统疾病患者或没有GAD抗体的SPS患者有作用仍不清楚。
Introduction High-titre anti-GAD antibodies are characteristically seen in patients with stiff person syndrome (SPS). Other CNS disorders, rarely associated with high anti-GAD antibody titres, include: a) SPS-plus, a syndrome characterised by SPS and cerebellar ataxia; b) Batten's disease; and c) rare patients with epilepsy and idiopathic cerebellar ataxia. Currently, high-titre anti-GAD antibodies serve only as markers of an autoimmune process within the CNS because their pathogenic role in the afore-mentioned disorders has not been established. In SPS, there is evidence of autoimmune pathogenesis based on: the association of the disease with other autoimmune disorders or autoantibodies; immunogenetic background; presence of oligoclonal IgG bands in the CSF with increased intrathecal anti-GAD antibody synthesis and response to immunotherapies. SPS is the only GAD-positive CNS disease where a controlled study with immunotherapy has been conducted.Methods Sixteen anti-GAD antibody-positive patients were randomised to receive IVIg or placebo for 3 months. After a washout, they crossed to the alternative therapy for another three months. Efficacy was based on the difference in scores of the distribution of stiffness index and heightened sensitivity (spasms) from baseline to the second and third month of the infusions. Direct treatment and carry-over effect were compared for both groups.Results The stiffness scores in the IVIg-randomised patients declined significantly from month 1 through 4, but rebounded when they crossed to placebo. In contrast, the scores in the placebo-randomised group remained constant from month 1-4 but dropped significantly after crossing to IVIg. Eleven patients who received IVIg became able to walk unassisted, stopped falling and assumed household or work duties. The duration of benefit varied from 6-12 weeks or up to a year. The antiGAD(65) antibody titres declined after IVIg, but not after placebo.Conclusion Based on a controlled study, IVIg is a safe and effective therapy for SPS in patients unresponsive to other agents. Whether IVIg has a role in the other GAD-positive patients with neurological disease, or in SPS patients without GAD antibodies, remains unknown.