Intravenous immunoglobulin (IVIg) has been used to treat inflammatory demyelinating diseases such as chronic inflammatory demyelinating polyneuropathy, Guillain-Barré syndrome, and multifocal motor neuropathy. Despite studies demonstrating the clinical effectiveness of IVIg, the mechanisms underlying its effects remain to be elucidated in detail. Herein, we examined the effects of IVIg on lysolecithin-induced demyelination of the sciatic nerve in a mouse model. Mice -administered with IVIg 1 and 3 days post-injection (dpi) of lysolecithin -exhibited a significantly decreased demyelination area at 7 dpi. Immunoblotting analysis using two different preparations revealed that IVIg reacted with a 36-kDa membrane glycoprotein in the sciatic nerve. Subsequent analyses of peptide absorption identified the protein as a myelin protein in the peripheral nervous system (PNS) known as large myelin protein zero (L-MPZ). Moreover, injected IVIg penetrated the demyelinating lesion, leading to deposition on L-MPZ in the myelin debris. These results indicate that IVIg may modulate PNS demyelination, possibly by binding to L-MPZ on myelin debris.
Keywords: demyelination; intravenous immunoglobulin (IVIg); large myelin protein zero (L-MPZ); lysophosphatidylcholine (lysolecithin); neuropathy; peripheral nerve.