Vernino S, Lennon V A
Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA.
Ann Neurol. 2000 Mar;47(3):297-305.
Neuron-restricted autoantibodies are important markers of neurological autoimmunity related to cancer. We identified a new paraneoplastic IgG, PCA-2 (Purkinje cell cytoplasmic antibody type 2), in 10 patients. Nine had mixed subacute neurological presentations (5 brainstem or limbic encephalitis, 3 cerebellar ataxia, 2 Lambert-Eaton myasthenic syndrome, 1 autonomic neuropathy, and 1 motor neuropathy). All 9 were smokers, and 8 had definite or probable lung cancer (7 with biopsy-confirmed small cell lung carcinoma [SCLC]; 1 imaged only). One patient had no follow-up information. A 10th patient was among 58 with uncomplicated SCLC. PCA-2 binds to a cytoplasmic antigen in neurons and SCLC cells. Its immunostaining pattern in mouse tissues is distinct from that of the paraneoplastic autoantibodies PCA-1 (anti-Yo, marker of immune response initiated by ovarian or breast carcinoma) and PCA-Tr (anti-Tr, immune response marker of Hodgkin's lymphoma). PCA-2 binds to cerebellar Purkinje somata and dendrites, neurons in internal granular layer and dentate nucleus, and neuronal elements in gut and kidney. Western blots of reduced/denatured cerebellar and SCLC proteins reveal a common antigenic band, of approximately 280 kd. PCA-2 is the seventh IgG neuronal autoantibody marker of paraneoplastic autoimmunity identifiable unambiguously by standardized immunofluorescence criteria.
神经元限制性自身抗体是与癌症相关的神经自身免疫的重要标志物。我们在10例患者中鉴定出一种新的副肿瘤性IgG，即PCA-2（2型浦肯野细胞胞质抗体）。9例患者有混合性亚急性神经症状（5例脑干或边缘性脑炎、3例小脑共济失调、2例兰伯特-伊顿肌无力综合征、1例自主神经病变和1例运动神经病变）。这9例患者均为吸烟者，8例有明确或可能的肺癌（7例经活检证实为小细胞肺癌[SCLC]；1例仅做了影像学检查）。1例患者没有随访信息。第10例患者是58例无并发症的SCLC患者之一。PCA-2与神经元和SCLC细胞中的一种胞质抗原结合。其在小鼠组织中的免疫染色模式与副肿瘤性自身抗体PCA-1（抗Yo，卵巢或乳腺癌引发免疫反应的标志物）和PCA-Tr（抗Tr，霍奇金淋巴瘤的免疫反应标志物）不同。PCA-2与小脑浦肯野细胞的胞体和树突、内颗粒层和齿状核中的神经元以及肠道和肾脏中的神经元件结合。还原/变性小脑和SCLC蛋白的蛋白质印迹显示一条约280kd的共同抗原带。PCA-2是通过标准化免疫荧光标准可明确鉴定的第七种副肿瘤性自身免疫性IgG神经元自身抗体标志物。
