Serum IgG antibodies to P0 dimer and 35 kDa P0 related protein in neuropathy associated with monoclonal gammopathy.

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.

 

Auteurs Bordeaux Neurocampus