Antibodies to contactin-1 in chronic inflammatory demyelinating polyneuropathy
Antibodies to contactin-1 in chronic inflammatory demyelinating polyneuropathy
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DOI：
10.1002/ana.23794
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发表时间：
2013-03-01
影响因子：
11.2
通讯作者：
Illa, Isabel
中科院分区：
文献类型：
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作者：
Querol, Luis;Nogales-Gadea, Gisela;Illa, Isabel
目的慢性炎症性脱髓鞘多神经根神经病(CIDP)是一种常见的自身免疫性神经病，临床表现各异。临床和实验证据表明，自身抗体可能参与了该病的发病，但靶抗原尚不清楚。轴突连接蛋白已被认为是候选抗原。我们检测了CIDP患者血清对神经元抗原的反应性，并使用免疫沉淀法进行抗原解离。方法采用原代培养的海马神经元，筛选出与神经元细胞表面有较强反应性的患者血清。通过免疫沉淀和质谱学确定了这些抗原的身份，随后通过细胞分析、大鼠坐骨神经损伤的免疫组织化学和免疫吸收实验证实了这些抗原的存在。结果46份CIDP患者血清中有4份与海马神经元和周围神经结旁结构呈强阳性反应(8.6%)。两名患者的血清沉淀了接触蛋白-1(CNTN1)，1名患者的血清同时沉淀了CNTN1和联系蛋白相关蛋白1(CASPR1)。有2例与CNTN1有反应，而第三例仅在CNTN1和CASPR1共转染时才有反应。没有其他CIDP患者或104名患有其他神经系统疾病的对照组检测呈阳性。所有3名患者都有共同的临床特征，包括高龄，以运动受累为主，出现攻击性症状，早期轴突受累，以及静脉注射免疫球蛋白反应差。针对CNTN1/CASPR1复合体的解释性抗体存在于具有共同临床特征的CIDP患者的亚群中。这一生物标志物的发现可能有助于解释这些患者的症状和对CIDP治疗的异质性反应。《安·神经》2013年；73：370380
Objective Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a frequent autoimmune neuropathy with a heterogeneous clinical spectrum. Clinical and experimental evidence suggests that autoantibodies may be involved in its pathogenesis, but the target antigens are unknown. Axoglial junction proteins have been proposed as candidate antigens. We examined the reactivity of CIDP patients' sera against neuronal antigens and used immunoprecipitation for antigen unraveling. Methods Primary cultures of hippocampal neurons were used to select patients' sera that showed robust reactivity with the cell surface of neurons. The identity of the antigens was established by immunoprecipitation and mass spectrometry, and subsequently confirmed with cell-based assays, immunohistochemistry with teased rat sciatic nerve, and immunoabsorption experiments. Results Four of 46 sera from patients with CIDP reacted strongly against hippocampal neurons (8.6%) and paranodal structures on peripheral nerve. Two patients' sera precipitated contactin-1 (CNTN1), and 1 precipitated both CNTN1 and contactin-associated protein 1 (CASPR1). Reactivity against CNTN1 was confirmed in 2 cases, whereas the third reacted only when CNTN1 and CASPR1 were cotransfected. No other CIDP patient or any of the 104 controls with other neurological diseases tested positive. All 3 patients shared common clinical features, including advanced age, predominantly motor involvement, aggressive symptom onset, early axonal involvement, and poor response to intravenous immunoglobulin. Interpretation Antibodies against the CNTN1/CASPR1 complex occur in a subset of patients with CIDP who share common clinical features. The finding of this biomarker may help to explain the symptoms of these patients and the heterogeneous response to therapy in CIDP. ANN NEUROL 2013;73:370380