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实验性变应性神经炎中的抗体库:PMP - 22作为一种新型神经原的证据。

The antibody repertoire in experimental allergic neuritis: evidence for PMP-22 as a novel neuritogen.

作者信息

Koehler N K, Martin R, Wiethölter H

机构信息

Department of Neurology, University of California at San Francisco 94143-0435, USA.

出版信息

J Neuroimmunol. 1996 Dec;71(1-2):179-89. doi: 10.1016/s0165-5728(96)00141-5.

Abstract

Experimental allergic neuritis (EAN) is an autoimmune disease that serves as an animal model for the Guillain-Barré syndrome (GBS). In both disorders there is still great uncertainty as to the significance and diversity of autoantibodies involved. We focused on the characterization of serum antibody production in response to various peripheral nervous system (PNS) myelin proteins during the course of actively induced EAN in Lewis rats. These data were compared with EAN induced by adoptive transfer of P2-specific CD4+ T cells (AT-EAN) and with inoculation with complete Freund's adjuvant (CFA) alone. Semiquantitative Western blotting was applied to measure serum IgM and IgG titers against specific myelin proteins, including P2, P0, myelin basic protein (MBP), myelin-associated glycoprotein (MAG) and PMP-22. Considerable differences in the dynamics of antibody titers against individual myelin proteins were observed in active EAN and after inoculation with CFA alone. Our data suggest a pathogenic role of IgM antibodies against HNK adhesion carbohydrate epitope expressing PNS proteins P0, MAG and PMP-22. Among these, PMP-22, a novel candidate neuritogen may be of particular relevance. Thus, we provide evidence for the involvement of antibody-mediated immune response in actively induced EAN and a basis for similar studies on related human disorders such as GBS or other demyelinating neuropathies.

摘要

实验性变应性神经炎(EAN)是一种自身免疫性疾病,可作为吉兰 - 巴雷综合征(GBS)的动物模型。在这两种疾病中,关于所涉及自身抗体的意义和多样性仍存在很大的不确定性。我们重点研究了在Lewis大鼠主动诱导EAN过程中,血清抗体对各种外周神经系统(PNS)髓鞘蛋白产生的反应特征。将这些数据与通过P2特异性CD4 + T细胞过继转移诱导的EAN(AT - EAN)以及单独接种完全弗氏佐剂(CFA)诱导的EAN进行比较。应用半定量蛋白质印迹法测量血清中针对特定髓鞘蛋白的IgM和IgG滴度,这些蛋白包括P2、P0、髓鞘碱性蛋白(MBP)、髓鞘相关糖蛋白(MAG)和PMP - 22。在主动诱导的EAN和单独接种CFA后,观察到针对单个髓鞘蛋白的抗体滴度动态存在显著差异。我们的数据表明,针对表达PNS蛋白P0、MAG和PMP - 22的HNK黏附碳水化合物表位的IgM抗体具有致病作用。其中,新型候选神经原PMP - 22可能具有特别重要的意义。因此,我们为抗体介导的免疫反应参与主动诱导的EAN提供了证据,并为针对GBS或其他脱髓鞘性神经病等相关人类疾病的类似研究奠定了基础。

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