Antineural Autoantibodies in Patients With Paraneoplastic Cerebellar Degeneration

副肿瘤性小脑变性患者的抗神经自身抗体

• 批准号: 63570358
• 负责人: TSUKAMOTO Tetsuro
• 金额: $ 1.34万
• 依托单位: Fukushima Medical College (1989)Tohoku University (1988)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1989
• 资助国家: 日本
• 起止时间: 1989 至 无数据
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-63570358/
• 关键词: Paraneoplastic cerebellar degeneration; Antineural autoantibody; Malignant tumor; Anti-Purkinje cell antibody; cDNA cloning

We studied serum autoantibodies from six patients with paraneoplastic cerebellar degeneration using rat brains. Immunohistochemically, serum samples from four of six patients with uterine or overian tumors showed a similar staining pattern, labeling Purkinje cells and various other neurons distributed throughout the brain and spinal cord. The immunoblot study showed that these serum samples recognized the common 52- kd band. Serum from a patient with duct carcinoma of the breast reacted with the 46- kd band with a similar but weaker immunohistochemical reactivity. Serum from another patient with small-cell carcinoma of the lung in whom paraneoplastic cerebellar degeneration and Eaton-Lambert myasthenic syndrome developed recognized the 40-kd and 38-kd bands with a different imunostaining pattern. Autoantibodies in patients with paraneoplastic cerebellar degeneration are directed to a variety of neuronal antigens that may differ from patient to patient.We isolated a cDNA clone encoding … More a 52-kd protein recognized by an anti-Purkinje cell antibody in the serum from a patient with paraneoplastic cerebellar degeneration associated with uterine carcinoma. The recombinant protein expressed in prokaryotic cells was specifically recognized by the anti-Purkinje cell antibody from the patient and its molecular weight was identical with that of antigenic protein in the cerebellum. The deduced protein consisted of 450 amino acids dominated by hydro- philic residues, the calculated relative molecular mass was 51238 and the predicted value of the isoelectric point was 4.99. This cDNA sequence and the deduced protein sequence have not been reported previously and showed no homologies with the cDNA or the amino acid sequences in the GenBank, EMBL or NBRF databases, including the cDNA for a 34-kd cerebellar protein (CDR34) which is recognized by an anti-Purkinje cell antibody. Unexpectedly, the transcript of this gene was detected not only in the cerebellum and the brain stem, but also in an extraneural tissue, the intestine. Less

我们用大鼠脑检测了6例副肿瘤小脑变性患者的血清自身抗体。免疫组织化学分析显示，6例子宫或卵巢肿瘤患者中有4例的血清样本显示出类似的染色模式，标记了分布在大脑和脊髓中的浦肯野细胞和各种其他神经元。免疫印迹研究表明，这些血清样本识别共同的52- kd带。一个乳腺导管癌患者的血清与46- kd带有相似但较弱的免疫组织化学反应。另一例伴副肿瘤小脑变性和伊顿-兰伯特肌无力综合征的肺小细胞癌患者血清以不同的免疫染色模式识别出40-kd和38-kd条带。副肿瘤小脑变性患者的自身抗体指向多种神经元抗原，这些抗原可能因患者而异。从子宫癌伴副肿瘤性小脑变性患者血清中分离出一种被抗浦肯野细胞抗体识别的52-kd蛋白的cDNA克隆。原核细胞中表达的重组蛋白被患者的抗浦肯野细胞抗体特异性识别，其分子量与小脑中的抗原蛋白相同。该蛋白由450个以亲水残基为主的氨基酸组成，计算得到的相对分子质量为51238，等电点预测值为4.99。该cDNA序列和推导出的蛋白序列此前未见报道，与GenBank、EMBL或NBRF数据库中的cDNA或氨基酸序列无同源性，包括抗浦肯野细胞抗体识别的34-kd小脑蛋白（CDR34）的cDNA。出乎意料的是，该基因的转录本不仅在小脑和脑干中被检测到，而且在神经外组织肠中也被检测到。少