Favereaux A, Lagueny A, Vital A, Schmitter J-M, Chaignepain S, Ferrer X, Labatut-Cazabat I, Vital C, Petry K G
Laboratoire de Neurobiologie des affections de la myeline EA2966, Bordeaux, France.
J Neurol Neurosurg Psychiatry. 2003 Sep;74(9):1262-6. doi: 10.1136/jnnp.74.9.1262.
Peripheral neuropathies (PN) associated with monoclonal gammopathy (MG) are widely considered as autoimmune disorders, but the putative role of incriminated antigens is still not understood.
Fifty five patients with PN associated with MG were studied to investigate whether new antigens could be found, and to evaluate their relation to clinical manifestations.
An immunological study was conducted on patient sera to identify autoreactivities against nerve proteins by western blotting. Antigen proteins were purified and analysed by proteomic tools. Correlation with ultrastrucural and clinical features was then studied.
Of the 55 patients suffering from PN associated with MG, 17 exhibited IgG autoantibodies directed against peripheral nerve proteins of 35, 58, and 60 kDa. N-terminal microsequencing and mass spectrometry analyses of the 35 kDa protein revealed perfect peptidic matching with 47% of the amino acid sequence of P0, whereas the 58 and 60 kDa proteins were identified as the reduced and non-reduced forms of a P0 dimer. Deglycosylation did not affect IgG binding to the 35 kDa P0 related protein, suggesting a peptidic epitope. In contrast, deglycosylation abolished IgG recognition of the P0 dimer protein, so that a carbohydrate moiety may be implicated in the epitope formation. This confirmed the existence of two different types of IgG, one recognising the 58 and 60 kDa proteins and one directed against the 35 kDa protein.
This is the first report of antibody activity directed against the dimeric association of P0. Although P0 oligomerisation and adhesion properties play a crucial part in the myelin sheath compaction, the pathogenic significance of these autoantibodies needs further investigations to be elucidated.
与单克隆丙种球蛋白病（MG）相关的周围神经病（PN）被广泛认为是自身免疫性疾病，但所涉及抗原的假定作用仍不清楚。
对55例与MG相关的PN患者进行研究，以调查是否能发现新抗原，并评估它们与临床表现的关系。
对患者血清进行免疫学研究，通过蛋白质印迹法鉴定针对神经蛋白的自身反应性。纯化抗原蛋白并用蛋白质组学工具进行分析。然后研究其与超微结构和临床特征的相关性。
在55例与MG相关的PN患者中，有17例表现出针对35、58和60 kDa周围神经蛋白的IgG自身抗体。对35 kDa蛋白的N端微测序和质谱分析显示，其肽段与P0氨基酸序列的47%完美匹配，而58和60 kDa蛋白被鉴定为P0二聚体的还原形式和非还原形式。去糖基化不影响IgG与35 kDa P0相关蛋白的结合，提示存在肽表位。相反，去糖基化消除了IgG对P0二聚体蛋白的识别，因此碳水化合物部分可能参与表位形成。这证实了存在两种不同类型的IgG，一种识别58和60 kDa蛋白，另一种针对35 kDa蛋白。
这是关于针对P0二聚体结合的抗体活性的首次报道。尽管P0寡聚化和黏附特性在髓鞘紧密化中起关键作用，但这些自身抗体的致病意义仍需进一步研究阐明。
