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  • Title: Anti-myelin-associated glycoprotein antibodies alter neurofilament spacing.
    Author: Lunn MP, Crawford TO, Hughes RA, Griffin JW, Sheikh KA.
    Journal: Brain; 2002 Apr; 125(Pt 4):904-11. PubMed ID: 11912122.
    Abstract:
    Axon calibre is crucial to efficient impulse transmission in the peripheral nervous system. Neurofilament numbers determine gross axonal diameter, but intra-axonal distribution depends on the phosphorylation status of neurofilament sidearms. Myelin-associated glycoprotein (MAG) has been implicated in the signalling cascade controlling neurofilament phosphorylation and hence in the control of axon calibre. In an electron microscopic morphometric study we measured nearest neighbour neurofilament distances (NNND) in the axons of sural nerves from patients with anti-MAG paraproteinaemic neuropathies and compared these with normal human sural nerves and those from patients with Guillain-Barré syndrome or chronic inflammatory demyelinating polyradiculoneuropathy. Axon calibre was similar in all groups. In normal human sural nerves, axonal NNND was correlated with axonal diameter (r = 0.56). In diseased axons this correlation did not exist. The NNND was significantly reduced in demyelinated axons (30.5+/-2.2 nm) and those with widely spaced myelin (28.9+/-1.3 nm) from patients with anti-MAG antibodies compared with normal axons from normal patients (39.8+/- 3.2 nm) or those with demyelinating neuropathy (35.8+/-4.6 nm). This reinforces the hypothesis that MAG is involved in the control of neurofilament spacing through sidearm phosphorylation and demonstrates a MAG-mediated pathogenic effect of the anti-MAG antibody in peripheral nerves.
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