Antoine J C, Absi L, Honnorat J, Boulesteix J M, de Brouker T, Vial C, Butler M, De Camilli P, Michel D
Neurology Service, Hôpital de Bellevue, Saint-Etienne, France.
Arch Neurol. 1999 Feb;56(2):172-7. doi: 10.1001/archneur.56.2.172.
Antiamphiphysin antibodies react with a 128-kd protein found in synaptic vesicles. They were first described in patients with paraneoplastic stiff-man syndrome and breast cancer, but studies suggest that they can also occur in patients with other tumors and neurological disorders.
To determine if antiamphiphysin antibodies are associated with various paraneoplastic neurological syndromes and tumors.
Of 2800 serum samples tested by routine immunohistochemical procedures on sections of paraformaldehyde-fixed rat brain for the detection of autoantibodies associated with paraneoplastic neurological syndromes, 5 were selected because of labeling suggestive of antiamphiphysin antibodies and subsequently confirmed by the results of Western blot analysis using recombinant amphiphysin protein. Controls consisted of 40 patients with various nonparaneoplastic neurological diseases; 101 patients with cancer but without paraneoplastic neurological syndrome; 9 patients with small cell lung cancer, anti-Hu antibodies, and paraneoplastic neurological syndrome; 3 patients with M2-type antimitochondrial antibodies but no neurological disorder; and 30 normal subjects.
Of the 5 patients with antiamphiphysin antibodies, patient 1 had sensory neuronopathy, encephalomyelitis, and breast cancer; patient 2 had limbic encephalitis, and small cell lung cancer was detected in the mediastinum after 24 months of follow-up; patient 3 had encephalomyelitis and ovarian carcinoma; and patients 4 and 5 had Lambert-Eaton myasthenic syndrome and small cell lung cancer (patient 4 subsequently developed cerebellar degeneration). None of the 5 had stiffness. Two patients (Nos. 2 and 4) had antimitochondrial antibodies. The two patients (Nos. 4 and 5) with Lambert-Eaton myasthenic syndrome had antibodies directed against the voltage-gated calcium channel, and patient 2 subsequently developed anti-Hu antibodies. In the controls, antiamphiphysin antibodies were detected by Western blot analysis in 3 of 8 patients with anti-Hu antibodies, but in none of the other groups.
These data indicate that antiamphiphysin antibodies are not specific for one type of tumor or one neurological syndrome and can be associated with other neural and nonneural antibodies. The simultaneous association of several antibodies in some patients suggests multimodal autoantibody production.
抗 amphiphysin 抗体与突触小泡中发现的一种 128-kd 蛋白发生反应。它们最初在副肿瘤性僵人综合征和乳腺癌患者中被描述，但研究表明它们也可出现在其他肿瘤和神经系统疾病患者中。
确定抗 amphiphysin 抗体是否与各种副肿瘤性神经综合征和肿瘤相关。
在通过常规免疫组织化学方法检测的 2800 份血清样本中，用多聚甲醛固定的大鼠脑切片检测与副肿瘤性神经综合征相关的自身抗体，其中 5 份因标记提示抗 amphiphysin 抗体而被选中，随后通过使用重组 amphiphysin 蛋白的 Western 印迹分析结果得到证实。对照组包括 40 例患有各种非副肿瘤性神经疾病的患者；101 例患有癌症但无副肿瘤性神经综合征的患者；9 例患有小细胞肺癌、抗 Hu 抗体和副肿瘤性神经综合征的患者；3 例患有 M2 型抗线粒体抗体但无神经系统疾病的患者；以及 30 名正常受试者。
在 5 例抗 amphiphysin 抗体患者中，患者 1 患有感觉神经元病、脑脊髓炎和乳腺癌；患者 2 患有边缘性脑炎，随访 24 个月后在纵隔中检测到小细胞肺癌；患者 3 患有脑脊髓炎和卵巢癌；患者 4 和 5 患有 Lambert-Eaton 肌无力综合征和小细胞肺癌（患者 4 随后发展为小脑变性）。5 例患者均无僵硬症状。2 例患者（2 号和 4 号）有抗线粒体抗体。2 例患有 Lambert-Eaton 肌无力综合征的患者（4 号和 5 号）有针对电压门控钙通道的抗体，患者 2 随后出现抗 Hu 抗体。在对照组中，Western 印迹分析在 8 例抗 Hu 抗体患者中的 3 例检测到抗 amphiphysin 抗体，但在其他组中均未检测到。
这些数据表明抗 amphiphysin 抗体并非针对某一种肿瘤或某一种神经综合征具有特异性，并且可与其他神经和非神经抗体相关。一些患者中几种抗体的同时出现提示多模式自身抗体产生。
