An IgM anti-MBP Ab in a case of Waldenstrom's macroglobulinemia with polyneuropathy expressing an idiotype reactive with an MBP epitope immunodominant in MS and EAE
An IgM anti-MBP Ab in a case of Waldenstrom's macroglobulinemia with polyneuropathy expressing an idiotype reactive with an MBP epitope immunodominant in MS and EAE
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DOI：
10.1016/s0165-5728(00)00425-2
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发表时间：
2001-02-01
影响因子：
3.3
通讯作者：
Galin, FS
中科院分区：
文献类型：
--
作者：
Noerager, BD;Inuzuka, T;Galin, FS
在先前描述的Waldenstrom大球蛋白血症合并多神经病变的病例中，IgM/lambda单克隆抗体（mAb）与髓鞘碱性蛋白（MBP）高度反应。鉴于我们最近发现的一种小鼠lambda可变区基因产物V lambdax本身可以结合MBP并赋予MBP对Ab的反应性，我们研究了小鼠V lambdax与这种人类IgM/lambda抗MBP之间共享独特型的可能性。我们用间接ELISA方法鉴定了MBP反应性IgM/lambda的表位特异性。MBP的瓜氨酸化异构体称为C8，或MBP的肽片段作为包被抗原，而V lambdax的单特异性Ab作为次级Ab。患者的MBP反应性IgM/lambda被V lambdax特异性的Ab识别，并且与含有V lambdax结合的人MBP的小鼠单抗一样，不包含MBP-C8或其他常见的自身抗原，如DNA、甲状腺球蛋白或肌动蛋白。抗MBP反应性对MBP肽90-170具有选择性，对MBP肽84-96具有选择性。因此，患者的巨球蛋白和可能某些具有“V λ独特型”的其他人类Ab结合MBP肽残基84-96，这是多发性硬化症患者的免疫优势肽。这种结合可能参与与浆细胞异常或自身免疫相关的神经免疫疾病患者神经损伤的发病机制。(C) 2001 Elsevier Science B.V.版权所有
In a previously described case of Waldenstrom's Macroglobulinemia, complicated by polyneuropathy, the IgM/lambda monoclonal antibody (mAb) was highly reactive with myelin basic protein (MBP). Given our demonstration that V lambdax, a recently described murine lambda variable region gene product, can itself bind MBP as well as confer MBP reactivity to an Ab, the possibility of a shared idiotypy between murine V lambdax and this human IgM/lambda anti-MBP was investigated. We characterized the epitope specificity of the macroglobulinemia patients MBP-reactive IgM/lambda using indirect ELISA procedures with MBP. a citrullinated isomer of MBP termed C8, or peptide fragments of MBP as the coating antigens and monospecific Ab to V lambdax as the secondary Ab. The patient's MBP-reactive IgM/lambda was recognized by Ab specific for V lambdax and, like murine mAb containing V lambdax bound human MBP but not MBP-C8 nor other common autoantigens such as DNA, thyroglobulin, or actin. The anti-MBP reactivity was selective for MBP peptide 90-170 and preferentially recognized MBP peptide 84-96. Thus, the patient's macroglobulin and perhaps certain other human Ab with a 'V lambdax idiotype' bind to MBP peptide residues 84-96, an immunodominant peptide in multiple sclerosis patients. Such binding may be involved in the pathogenesis of neural damage in patients with neuroimmunologic disorders related to plasma cell dyscrasias or autoimmunity. (C) 2001 Elsevier Science B.V. All rights reserved.