Bacteria necessary to produce experimental autoimmune myasthenia gravis in acetylcholine receptor-immunised rabbits?

Abstract

WE have1–3 described previously a paralytic disease observed in rabbits immunised with small doses, in Freund's complete adjuvant, of nicotinic cholinergic receptor protein (nAChR) isolated from the electric organ of Torpedo marmorata. Decremental muscle response after nerve stimulation and positive effects of anticholinesterase administration, decrease in miniature endplate potential amplitude and increased curare sensitivity were similar to findings in patients suffering from myasthenia gravis. Nicotinic AChR antibody titres above 2–3 mg ml−1 have been found, the observed muscle decrement increasing with increasing antibody titre. Occasionally, variations in electromyographic activity were observed, suggesting denervation. Morphological analysis3,4 showed severe destruction of postsynaptic motor endplate areas and reduction of toxin-binding sites, followed by changes at the presynaptic side. A second stage of the disease was characterised by high sensitivity to nAChR injections and by the presence of motor endplates lacking secondary postsynaptic foldings. Our work and that of others (for review see ref. 5) suggests that an immune response to nAChR seems to be involved in the aetiology of experimental autoimmune myasthenia gravis (EAM) just as is suggested for human myasthenia gravis. The role of a humoral and/or cellular immune response and that of the thymus are under discussion5,6. The decremental response to repetitive nerve stimulation may be caused directly and/or indirectly by nAChR antibodies, whereas defects in electromyographic activity such as high frequency discharges and fibrillation action potentials which we have observed may have been caused by other, accompanying mechanisms. This report deals with the role of bacteria in EAM and with the relationship of the antibody titre to the electro-physiological findings.

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References

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    Heilbronn, E., and Mattsson, C., J. Neurochem., 22, 315 (1974).

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    Heilbronn, E., in Motor Innervation of Muscle (edit. by Thesleff, S.) (Academic, New York and London, in the press).

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    Lennon, V. A., Lindstrom, J. D., and Seybold, M. E., Ann. N.Y. Acad. Sci., 274 (1976).

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