Serum IgG antibodies to P0 dimer and 35 kDa P0 related protein in neuropathy associated with monoclonal gammopathy. Issue 9 (21st August 2003)

• Record Type: Journal Article
• Authors: Favereaux, A; Lagueny, A; Vital, A; Schmitter, J-M; Chaignepain, S; Ferrer, X; Labatut-Cazabat, I; Vital, C; Petry, K G
• Is Part Of: Journal of neurology, neurosurgery and psychiatry. Volume 74:Issue 9(2003)
• Page Start: 1262
• Page End: 1266
• Publication Date: 2003-08-21
• Subjects: myelin protein zero -- peripheral neuropathy -- monoclonal gammopathy -- P0 dimeric association; PN, peripheral neuropathies -- MG, monoclonal gammopathy -- MAG, myelin asociated glycoprotein -- PNS, peripehral nervous system; Neurology -- Periodicals; Nervous system -- Surgery -- Periodicals; Psychiatry -- Periodicals; 616.8
• DOI: 10.1136/jnnp.74.9.1262
• Languages: English
• ISSNs: 0022-3050

Abstract

Abstract : Background: 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. Objective: 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. Methods: 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. Results: 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. Conclusions: 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.