Experimental induction of myelin changes by anti-MAG antibodies and terminal complement complex

Salvatore Monaco, Sergio Ferrari, Bruno Bonetti, Giuseppe Moretto, Michael Kirshfink, Ettore Nardelli, Eduardo Nobile-Orazio, Gianluigi Zanusso, Nicola Rizzuto, Francesco Tedesco

Research output: Contribution to journalArticle

Abstract

We investigated the role of anti-myelin-associated glycoprotein (MAG) IgM and complement (C) in the pathogenesis of myelin alterations occurring in patients with anti-MAG-associatcd polyneuropathy. For this purpose, we separately studied the effects of anti-MAG antibodies and terminal C complex (TCC) after injection into the rabbit sciatic nerve. The two different local treatments produced identical ultrastructural abnormalities such as intramyclinic edema, myelin vesiculation and, in particular, separation of the major dense lines with the formation of widely spaced myelin, a peculiar feature encountered in human peripheral nerve disorders with circulating anti-myelin monoclonal IgM. In nerves treated with anti-MAG IgM ultrastructural myelin alterations were concurrent with activation of the rabbit's own C to the formation of TCC. Contrary to the immunological and ultrastructural findings obtained in C-sufficient animals, in C6-deficicnt rabbits injected with anti-MAG IgM no myelin alterations nor C completion were observed. This study identifies anti-MAG IgM as the mediator and the C as the effector of myelin changes observed in the present model and, for extension, in human neuropathies associated with anti-MAG IgM.

Original languageEnglish
Pages (from-to)96-104
Number of pages9
JournalJournal of Neuropathology and Experimental Neurology
Volume54
Issue number1
Publication statusPublished - 1995

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Keywords

  • C6-deficient rabbits
  • Intramyclinic edema
  • Myelin-associated glycoprotein
  • Terminal complement complex
  • Widely spaced myelin

ASJC Scopus subject areas

  • Clinical Neurology
  • Pathology and Forensic Medicine
  • Cellular and Molecular Neuroscience
  • Neurology
  • Neuroscience(all)

Cite this

Monaco, S., Ferrari, S., Bonetti, B., Moretto, G., Kirshfink, M., Nardelli, E., Nobile-Orazio, E., Zanusso, G., Rizzuto, N., & Tedesco, F. (1995). Experimental induction of myelin changes by anti-MAG antibodies and terminal complement complex. Journal of Neuropathology and Experimental Neurology, 54(1), 96-104.