SELECTIVE LOSS OF MYELIN-ASSOCIATED GLYCOPROTEIN FROM MYELIN CORRELATES WITH ANTI-MAG ANTIBODY TITER IN DEMYELINATING PARAPROTEINEMIC POLYNEUROPATHY

The IGM monoclonal autoantibodies of patients with demyelinating parap roteinaemic polyneuropathy recognize a carbohydrate structure present on both myelin-associated glycoprotein (MAG) and protein zero (P-0). T hese auto-antibodies are sufficient to cause the disease but the mecha nism of demyelination remains unclear. We have analysed nerve biopsies from eight patients with polyneuropathy and anti-MAG antibodies by qu antitative immunohistochemistry and find a concordant pattern of reduc ed expression of myelin markers with the loss of myelinated fibres. We report here novel features of this disease, in particular a selective lack of detectable MAG in a large proportion of myelinated fibres con taining P-0, myelin basic protein (MBP) and periaxin. There is also an inverse correlation of the distribution of MAG in peripheral nerve my elin with the serum anti-MAG antibody titres but no correlation of the se titres with the loss of myelinated fibres. Double immunofluorescenc e staining of paraproteinaemic polyneuropathy (PPN) nerves shows anti- MAG IgM deposited on the periphery of myelinated fibres associated wit h or lacking MAG staining. These data suggest that the binding of anti -MAG antibodies to MAG and/or other myelin component(s) results in MAG downregulation and may have an essential role in the molecular mechan isms leading to demyelination adn partial regeneration in this disease .