Qualitative and quantitative evidence of anti-glutamic acid decarboxylase-specific intrathecal antibody synthesis in patients with stiff person syndrome
Qualitative and quantitative evidence of anti-glutamic acid decarboxylase-specific intrathecal antibody synthesis in patients with stiff person syndrome
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DOI：
10.1016/j.jneuroim.2010.07.019
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发表时间：
2010-12-15
影响因子：
3.3
通讯作者：
Rauer, S.
中科院分区：
文献类型：
--
作者：
Jarius, S.;Stich, O.;Rauer, S.
背景资料：僵直人综合征（SPS）是一种以严重强直和痉挛为特征的中枢神经系统疾病，其病因可能为自身免疫性疾病。在大多数情况下，SPS与抗谷氨酸脱羧酶（GAD-Ab）的血清抗体相关。近年来的研究表明GAD-Ab可能直接参与了SPS的发病过程。对这一假设的进一步支持将来自于为SPS患者的CNS内存在产生GAD-Ab的B细胞克隆提供定性证据的研究。为了解决这个问题，我们（i）通过抗原驱动的亲和印迹技术分析了来自10名GAD-Ab阳性SPS患者和对照组的成对脑脊液（CSF）和血清样品，以确定GAD-Ab的存在。特异性寡克隆IgG带（OCB）在CSF中，和（ii）研究了免疫反应模式的CSF和血清IgG重组GAD的免疫印迹。为了确认我们的结果定量，我们（iii）评估抗GAD抗体反应性CSF和血清中使用ELISA和评估的GAD特异性抗体index.Results：GAD特异性寡克隆带完全或主要在CSF中相比，相应的血清中检测到10/10例GAD阳性的SPS，但没有在控制。免疫印迹显示CSF中染色较强，提示鞘内IgG合成，在7/10例患者中目视检查，在8/10例患者中密度分析。在9/10例患者中发现了GAD特异性抗体阳性指数。结论：在这里，我们首次证明了SPS中的IgG OCB结合GAD。我们的研究结果有助于正在进行的讨论是否对GAD的自身免疫过程参与SPS的发病机制，表明抗GAD-Ab是由中枢神经系统内的B细胞克隆。(C)2010 Elsevier B. V.保留所有权利。
Background: The stiff person syndrome (SPS) is a CNS disorder of putative autoimmune aetiology, which is clinically characterized by severe rigidity and spasms. In most cases, SPS is associated with serum antibodies against glutamic acid decarboxylase (GAD-Ab). Recent studies suggested that GAD-Ab might be directly involved in the pathogenesis of SPS. Further support for this hypothesis would come from studies providing qualitative evidence for the presence of GAD-Ab-producing B cell clones within the CNS of patients with SPS.Objective and methods: To address that issue, we (i) analysed paired cerebrospinal fluid (CSF) and serum samples from ten GAD-Ab positive patients with SPS and controls by an antigen-driven affinity blotting technique for the presence of GAD-specific oligoclonal IgG bands (OCBs) in the CSF, and (ii) examined the immunoreactive pattern of CSF and serum IgG to recombinant GAD by immunoblotting. To confirm our results quantitatively, we (iii) assessed anti-GAD antibody reactivity in CSF and serum using ELISA and evaluated the GAD-specific antibody index.Results: GAD-specific oligoclonal bands exclusively or predominately in CSF compared to the corresponding serum were detected in 10/10 patients with GAD-positive SPS but in none of the controls. Immunoblotting revealed stronger staining in the CSF, suggestive of intrathecal IgG synthesis, in 7/10 patients upon visual inspection, and in 8/10 patients upon densitometric analysis. A positive GAD-specific antibody index was found in 9/10 patients.Conclusions: Here we demonstrate for the first time that IgG OCBs in SPS bind GAD. Our findings contribute to the ongoing discussion on whether the autoimmune process against GAD is involved in the pathogenesis of SPS by indicating that anti-GAD-Ab is produced by B cell clones within the CNS. (C) 2010 Elsevier B.V. All rights reserved.