Antineural Autoantibodies in Patients With Paraneoplastic Cerebellar Degeneration

我们用大鼠脑研究了6例副肿瘤性小脑变性患者的血清自身抗体。免疫组织化学显示，6例子宫或卵巢肿瘤患者中有4例的血清样本显示了类似的染色模式，标记了浦肯野细胞和分布在大脑和脊髓的各种其他神经元。免疫印迹研究表明，这些血清样本识别共同的52-kd条带。乳腺导管癌患者的血清与46-kd条带反应类似，但免疫组织化学反应较弱。另一例肺小细胞癌副肿瘤性小脑变性和Eaton-Lambert肌无力综合征患者的血清以不同的免疫染色模式识别40kd和38kd条带。副肿瘤性小脑变性患者的自身抗体针对不同患者的多种神经元抗原。我们分离了一个编码…的cDNA克隆More是一种52kd的蛋白，可被抗浦肯野细胞抗体识别，该蛋白来自与子宫癌相关的副肿瘤性小脑变性患者。在原核细胞中表达的重组蛋白可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。推导的蛋白质由450个氨基酸组成，以亲水残基为主，计算的相对分子质量为51238，等电点预测值为4.99。该序列和推导出的蛋白序列与GenBank、EMBL或NBRF数据库中的cDNA或氨基酸序列没有同源性，包括34kd小脑蛋白(CDR34)的cDNA，该蛋白可被抗浦肯野细胞抗体识别。出乎意料的是，不仅在小脑和脑干中检测到该基因的转录本，而且在神经外组织--肠道中也检测到了该基因的转录本。较少

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