High definition profiling of autoantibodies to glutamic acid decarboxylases GAD65/GAD67 in stiff-person syndrome
High definition profiling of autoantibodies to glutamic acid decarboxylases GAD65/GAD67 in stiff-person syndrome
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DOI：
10.1016/j.bbrc.2007.11.077
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发表时间：
2008-02-01
影响因子：
3.1
通讯作者：
Iadarola, Michael J.
中科院分区：
文献类型：
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作者：
Burbelo, Peter D.;Groot, Sandra;Iadarola, Michael J.
用于诊断神经系统疾病的高度可靠的生物标志物尚未广泛使用。在这里，我们评估了用于诊断中枢神经系统自身免疫性疾病、僵人综合征 (SPS) 的荧光素酶免疫沉淀技术 (LIPS)。通过 LIPS 对来自 SPS 和对照受试者的 40 份血清样本进行抗 GAD65 抗体分析，发现显着的滴度差异，使得 SPS 的诊断具有 100% 的敏感性和 100% 的特异性。 SPS的抗GAD65抗体滴度与对照受试者分离，其值比对照受试者平均值高出23个标准差以上。通过分析患者抗体对 GAD65 亚片段的直接反应，含有脱羧酶催化结构域的中心区域与所有 SPS 血清均具有高度免疫反应性，而 N 端和 C 端区域显示出较低的抗体滴度，并且仅与 SPS 血清的子集发生反应。额外的分析显示，一些 SPS 患者表现出针对 GAD67 和酪氨酸羟化酶的自身抗体，但未检测到半胱氨酸亚磺酸脱羧酶或 GABA 转氨酶的显着免疫反应性。这项研究验证了 LIPS 是一种检测自身抗体以诊断 SPS 和潜在其他神经系统疾病的可靠方法。由爱思唯尔公司出版
Highly reliable biomarkers for the diagnosis of neurological diseases are not widely available. Here we evaluated a luciferase immunoprecipitation technology (LIPS) for the diagnosis of a CNS autoimmune disorder, stiff-person syndrome (SPS). Analysis by LIPS of 40 sera samples from SPS and control subjects for anti-GAD65 antibodies revealed dramatic titer differences allowing diagnosis of SPS with 100% sensitivity and 100% specificity. Anti-GAD65 antibody titers of SPS were segregated from controls with values greater than 23 standard deviations above the control subject mean. By analyzing patient antibody responses directly to GAD65 sub-fragments, the central region containing the decarboxylase catalytic domain was highly immunoreactive with all of the SPS sera, while the N- and C-terminal regions showed lower antibody titers and only reacted with subsets of SPS sera. Additional profiling revealed that some SPS patients showed autoantibodies against GAD67 and tyrosine hydroxylase, but no significant immunoreactivity was detected with cysteine sulfinic acid decarboxylase or GABA transaminase. This study validates LIPS as a robust method to interrogate autoantibodies for the diagnosis of SPS and potentially other neurological diseases. Published by Elsevier Inc.