Morphological changes at paranodes in IgM paraproteinaemic neuropathy.
The paranode is one of a number of sites of a specific myelin sheath abnormality found in cases of IgM paraproteinaemic neuropathy. The gammopathy may be malignant or, more frequently, benign, and is often associated with a predominantly demyelinating neuropathy. The circulating paraprotein IgM antibody, usually with kappa light chains, was found in many cases to recognise an antigenic determinant in myelin, identified as myelin-associated glycoprotein (MAG). Other glycoconjugates expressed by Schwann cells may also be recognised by the antibody. MAG is localized to regions of the myelin sheath in which the membranes are uncompacted. The paranode is one such region, and there is evidence that IgM is deposited specifically on the membranes of the terminal loops of the myelin sheath in addition to other MAG-associated regions of the sheath. In many cases the presence of the paraprotein appears not to otherwise affect paranodal organization; in a few it is associated with changes to the termination of the loops on the axolemma and to the associated Schwann cell cytoplasm. These findings do not provide unambiguous evidence that binding of anti-MAG IgM antibodies at the paranode is a direct cause of demyelination. Whilst localization of the paraprotein closely matches that of MAG, proof is still lacking that the relevant antigen is MAG itself.
Jacobs
J M
JM
Department of Neuropathology, Institute of Neurology, London, United Kingdom.
D000818:Animals; D006801:Humans; D007075:Immunoglobulin M / Q000378:metabolism*; D018992:Myelin-Associated Glycoprotein / Q000032:analysis / Q000502:physiology; D010265:Paraproteinemias / Q000473:pathology*; D010523:Peripheral Nervous System Diseases / Q000473:pathology*; D011901:Ranvier's Nodes / Q000473:pathology*
D007075:Immunoglobulin M; D018992:Myelin-Associated Glycoprotein