Refractoriness to a second episode of experimental myasthenia gravis. Correlation with AChR concentration and morphologic appearance of the postsynaptic membrane

A. L. Corey, David P Richman, M. A. Agius, R. L. Wollmann

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Rats injected with anti-acetylcholine receptor (anti-AChR)2 monoclonal antibodies (mAb) develop the acute phase of experimental autoimmune myasthenia gravis characterized by a macrophage inflammation of muscle endplates (EP). These animals are subsequently refractory to induction of a second such episode up to 8 wk after the initial injection. Analysis of this phenomenon to date has shown that mechanisms such as anti-idiotypic regulation, epitopic modulation, and cellular suppression or deletion are not significantly involved. In the present study, animals reinjected from 11 wk on developed a second episode of cellular EP inflammation. This renewed susceptibility correlated temporally with an increase in postsynaptic membrane length and AChR content. When the second injection of anti-AChR mAb was given at 8 wk, mAb bound to muscle EP caused a small reduction in AChR content in the absence of cellular inflammation. These observations suggested that total inaccessibility of AChR to mAb is not responsible for the refractoriness to cellular EP inflammation. More likely, a certain AChR concentration or density is necessary to bind a critical amount or density of antibody to activate complement and set in motion the events leading to a cellular inflammatory response. In human myasthenia gravis, in which initially damaged EP are continuously exposed to anti-AChR antibodies, this critical AChR concentration or density may not be reached again because of continuous complement-mediated lysis and/or increased AChR turnover. Hence, these data may explain the infrequency of cellular EP inflammation in motor point muscle biopsies in this disease.

Original languageEnglish (US)
Pages (from-to)3269-3275
Number of pages7
JournalJournal of Immunology
Volume138
Issue number10
StatePublished - 1987
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

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