Role of complement in the pathogenesis of experimental autoimmune myasthenia gravis

Vanda A Lennon, M. E. Seybold, J. M. Lindstrom, C. Cochrane, R. Ulevitch

Research output: Contribution to journalArticle

183 Citations (Scopus)

Abstract

An acute phase of experimental autoimmune myasthenia gravis (EAMG) occurs transiently early in the immune response of Lewis rats to nicotinic acetylcholine receptors (AChR) when Bordetella pertussis is used as adjuvant. It is characterized by a destructive cellular attack directed at the postsynaptic membrane of muscle. Acute EAMG can be passively transferred to normal rats by IgG from serum of rats with chronic EAMG. In the present study, acute EAMG, induced either by passive transfer of syngeneic antibodies or by active immunization, was inhibited in rats depleted of complement by treatment with cobra venom factor (CoF). Furthermore, passive transfer of antibodies in excess of the muscle's content of AChR was without any measurable effect in rats treated with CoF. Although 60% of the muscle's AChR was complexed with antibody, there was no reduction in the muscle's content of AChR, and neuromuscular transmission was not compromised as judged electromyographically by curare sensitivity. These data imply that redistribution, accelerated degradation, and impairment of the ionophore function of AChR, effects of antibodies described in vitro on extrajunctional AChR, do not play a significant role in vivo in impairing neuromuscular transmission in an intact neuromuscular junction. Complement appears to be a critical mediator of anti-AChR antibodies' pathogenicity in vivo.

Original languageEnglish (US)
Pages (from-to)973-983
Number of pages11
JournalJournal of Experimental Medicine
Volume147
Issue number4
DOIs
StatePublished - 1978

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Autoimmune Experimental Myasthenia Gravis
Cholinergic Receptors
Muscles
Passive Immunization
Antibodies
Curare
Bordetella pertussis
Neuromuscular Junction
Ionophores
Nicotinic Receptors
Virulence
Vaccination
Immunoglobulin G
Membranes
Serum

ASJC Scopus subject areas

  • Immunology

Cite this

Role of complement in the pathogenesis of experimental autoimmune myasthenia gravis. / Lennon, Vanda A; Seybold, M. E.; Lindstrom, J. M.; Cochrane, C.; Ulevitch, R.

In: Journal of Experimental Medicine, Vol. 147, No. 4, 1978, p. 973-983.

Research output: Contribution to journalArticle

Lennon, Vanda A ; Seybold, M. E. ; Lindstrom, J. M. ; Cochrane, C. ; Ulevitch, R. / Role of complement in the pathogenesis of experimental autoimmune myasthenia gravis. In: Journal of Experimental Medicine. 1978 ; Vol. 147, No. 4. pp. 973-983.
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