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外周髓鞘P0蛋白一种可能的新型异构体:恶性淋巴瘤合并周围神经病患者体内自身抗体识别的靶抗原

A possible novel isoform of peripheral myelin P0 protein: a target antigen recognized by an autoantibody in a patient with malignant lymphoma and peripheral neuropathy.

作者信息

Ishida K, Takeuchi H, Takahashi R, Yoshimura K, Yamada M, Mizusawa H

机构信息

Department of Neurology, Tokyo Medical and Dental University Graduate School of Medicine, 1-5-45 Yushima, Tokyo 113-8519, Japan.

出版信息

J Neurol Sci. 2001 Jul 15;188(1-2):43-9. doi: 10.1016/s0022-510x(01)00547-0.

DOI:10.1016/s0022-510x(01)00547-0
PMID:11489284
Abstract

We tried to characterize a 35-kD antigen recognized by the serum IgG of a patient with malignant lymphoma and peripheral neuropathy. By Western blotting, the serum IgG reacted with the 35-kD antigen in the human, bovine and mouse peripheral nerve (PN) but not with other neural and non-neural tissues. Immunohistochemical analysis showed immunoreactivity of the IgG in the compact myelin of PN. We constructed a human sciatic nerve cDNA library and screened it using IgG of the patient. Three independent clones were obtained. Sequence alignment indicated that the inserts of these clones were homologous to the P0 cDNA, but that all three corresponded to the 3'-untranslational region of the P0 cDNA. To biochemically analyze the 35-kD antigen, myelin fractions of the human and bovine PN were prepared. The 35-kD antigen was purified from the crude myelin fraction by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. When the immunoreactivities of the 35-kD antigen for the IgG of the patient and a monoclonal anti-P0 antibody were compared with those of P0 protein for these antibodies, the 35-kD antigen reacted with both antibodies, but the P0 protein reacted with only the monoclonal anti-P0 antibody. These results suggest that the 35-kD antigen is an isoform of P0 protein. Although it is unlikely that the autoantibody may be the primary cause of neuropathy, because they were also detected in patients with lymphoma without overt neuropathy, they appear to be a modifying factor in the progression of neuropathy.

摘要

我们试图鉴定一种由恶性淋巴瘤合并周围神经病变患者血清IgG识别的35kD抗原。通过蛋白质印迹法,该患者血清IgG与人、牛和小鼠的周围神经(PN)中的35kD抗原发生反应,但与其他神经组织和非神经组织不发生反应。免疫组织化学分析显示IgG在PN的致密髓鞘中有免疫反应性。我们构建了一个人坐骨神经cDNA文库,并用该患者的IgG进行筛选。获得了三个独立的克隆。序列比对表明,这些克隆的插入片段与P0 cDNA同源,但所有三个克隆均对应于P0 cDNA的3'-非翻译区。为了对35kD抗原进行生化分析,制备了人和牛PN的髓鞘组分。通过十二烷基硫酸钠(SDS)-聚丙烯酰胺凝胶电泳从粗髓鞘组分中纯化35kD抗原。当将35kD抗原对该患者IgG和单克隆抗P0抗体的免疫反应性与P0蛋白对这些抗体的免疫反应性进行比较时,35kD抗原与两种抗体均发生反应,但P0蛋白仅与单克隆抗P0抗体发生反应。这些结果表明,35kD抗原是P0蛋白的一种异构体。尽管自身抗体不太可能是神经病变的主要原因,因为在没有明显神经病变的淋巴瘤患者中也检测到了它们,但它们似乎是神经病变进展中的一个修饰因素。

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A possible novel isoform of peripheral myelin P0 protein: a target antigen recognized by an autoantibody in a patient with malignant lymphoma and peripheral neuropathy.外周髓鞘P0蛋白一种可能的新型异构体:恶性淋巴瘤合并周围神经病患者体内自身抗体识别的靶抗原
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引用本文的文献

1
L-MPZ, a novel isoform of myelin P0, is produced by stop codon readthrough.L-MPZ,髓鞘 P0 的一种新型异构体,通过终止密码子通读产生。
J Biol Chem. 2012 May 18;287(21):17765-17776. doi: 10.1074/jbc.M111.314468. Epub 2012 Mar 28.
2
Serum IgG antibodies to P0 dimer and 35 kDa P0 related protein in neuropathy associated with monoclonal gammopathy.与单克隆丙种球蛋白病相关的神经病变中针对P0二聚体和35 kDa P0相关蛋白的血清IgG抗体
J Neurol Neurosurg Psychiatry. 2003 Sep;74(9):1262-6. doi: 10.1136/jnnp.74.9.1262.