Frequency of Synaptic Autoantibody Accompaniments and Neurological Manifestations of Thymoma
Frequency of Synaptic Autoantibody Accompaniments and Neurological Manifestations of Thymoma
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DOI：
10.1001/jamaneurol.2016.0603
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发表时间：
2016-07-01
期刊：
影响因子：
29
通讯作者：
Lennon, Vanda A.
中科院分区：
文献类型：
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作者：
Zekeridou, Anastasia;McKeon, Andrew;Lennon, Vanda A.
胸腺瘤通常被认为与副肿瘤性自身免疫性重症肌无力（MG）相关，MG是一种IgG介导的针对肌肉烟碱乙酰胆碱受体的突触传递障碍。新发现的突触自身抗体可能会扩大血清学资料的thymoma.Objective探讨潜在致病性神经突触自身抗体的频率在患者thymoma.DESIGN，SETTING，AND PARTICIPANTS我们回顾性地确定了患者与组织病理学证实的胸腺瘤和血清可用于测试突触自身抗体（收集1986-2014）在马约诊所神经免疫学实验室。我们将193例胸腺瘤患者分为4组：（1）无神经系统自身免疫（n = 43），（2）单纯MG（n = 98），（3）MG伴其他神经系统自身免疫表现（n = 26），（4）单纯MG（n = 28）。（4）MG以外的神经系统自身免疫（n = 26）主要结果和测量结果与肌肉、外周和中枢神经系统的分子定义的突触质膜蛋白反应的自身抗体的临床表现和血清谱。患者平均年龄为52岁，性别（106名女性）或组间无显著差异。重症肌无力是最常见的临床表现（64%），其次是自主神经功能障碍（16例患者[8%]）和脑病（15例患者[8%]）; 164例患者（85%）至少有1种突触自身抗体，其中63例患者（38%）至少有1种以上。肌肉乙酰胆碱受体最常见（78%），其次是神经节乙酰胆碱受体（20%），电压门控Kv 1钾通道复合物（13%）和α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体（5%）。不太常见的是水通道蛋白-4，电压门控Kv 1钾通道复合物相关蛋白（富含亮氨酸的胶质瘤失活蛋白1和接触素相关蛋白样2），甘氨酸受体，和。氨基丁酸-A受体结论和相关性突触自身抗体，特别是与配体门控烟碱乙酰胆碱受体超家族（即α-氨基-3-羟基-5-甲基-4-异恶唑丙酸、甘氨酸和α-氨基-3-羟基-5-甲基-4-异恶唑丙酸）的离子通道反应的突触自身抗体，氨基丁酸-A受体）在胸腺瘤患者中普遍存在。这种广谱的自身抗体可以增强自身免疫血清学检测，有助于胸腺瘤的术前诊断。检测目前已知的突触自身抗体特异性缺乏从这个配置文件有潜在的算法有用性作为胸腺瘤的阴性预测（如神经元电压门控钙通道自身抗体的认可）。
IMPORTANCE Thymoma is commonly recognized in association with paraneoplastic autoimmune myasthenia gravis (MG), an IgG-mediated impairment of synaptic transmission targeting the nicotinic acetylcholine receptor of muscle. Newly identified synaptic autoantibodies may expand the serological profile of thymoma.OBJECTIVE To investigate the frequency of potentially pathogenic neural synaptic autoantibodies in patients with thymoma.DESIGN, SETTING, AND PARTICIPANTS We retrospectively identified patients with histopathologically confirmed thymoma and serum available to test for synaptic autoantibodies (collected 1986-2014) at the Mayo Clinic Neuroimmunology Laboratory. We identified and classified 193 patients with thymoma into 4 groups: (1) lacking neurological autoimmunity (n = 43); (2) isolated MG(n = 98); (3) MG plus additional autoimmune neurological manifestations (n = 26); and (4) neurological autoimmunity other than MG(n = 26).MAIN OUTCOMES AND MEASURES Clinical presentation and serum profile of autoantibodies reactive with molecularly defined synaptic plasma membrane proteins of muscle, peripheral, and central nervous systems.RESULTS Of the 193 patients with thymoma, mean patient age was 52 years and did not significantly differ by sex (106 women) or group. Myasthenia gravis was the most prevalent clinical manifestation (64%) followed by dysautonomia (16 patients [8%]) and encephalopathy (15 patients [8%]); 164 patients (85%) had at least 1 synaptic autoantibody, and 63 of these patients (38%) had at least 1 more. Muscle acetylcholine receptor was most frequent (78%), followed by ganglionic acetylcholine receptor (20%), voltage-gated Kv1 potassium channel-complex (13%), and a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (5%). Less frequent were aquaporin-4, voltage-gated Kv1 potassium channel-complex related proteins (leucine-rich glioma-inactivated 1 and contactin-associated protein-like 2), glycine receptor, and.-aminobutyric acid-A receptor. Synaptic autoantibodies were significantly more frequent in patients with neurological autoimmunity than in those without and were most frequent in patients with neurological manifestations other than or in addition to MG.CONCLUSIONS AND RELEVANCE Synaptic autoantibodies, particularly those reactive with ion channels of the ligand-gated nicotinic acetylcholine receptor superfamily (namely a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, glycine, and.-aminobutyric acid-A receptors), were prevalent in patients with thymoma. Autoantibodies of this extended spectrum may enhance autoimmune serological testing as an aid to preoperative thymoma diagnosis. Detection of currently known synaptic autoantibody specificities absent from this profile have potential algorithmic usefulness as negative predictors for thymoma (as recognized for neuronal voltage-gated calcium channel autoantibodies).