Anti-(acetylcholine receptor) antibodies in myasthenia gravis.

  • Helen Sylvia Lotwick

Student thesis: Doctoral ThesisPhD


Levels of anti-(AChR) antibodies were determined in serial serum samples from 14 myasthenic patients over a period of several months, using detergent-solubilized muscle extracts of junctional rat AChR, extra-junctional rat AChR and human adult AChR as antigens. Anti-(AChR) antibody titres obtained using human adult AChR were always higher than those obtained using extra-junctional rat AChR, which were, in turn, always higher than those obtained using junctional rat AChR. Ihe ratios of antibody titres obtained by using the different antigens varied between patients, but were constant for an individual over the period of study. Complementary evidence for the same phenamenon was obtained by other experiments in which an excess of each serum was used to precipitate limited amounts of AChR from muscle extracts. The results obtained by conbining myasthenic sera argue against the suggestion that incomplete precipitation of receptor by certain sera is caused by the absence of particular antibody sub-populations. An alternative explanation, that sera precipitating low amounts of AChR contain toxin-releasing antibodies, is supported by direct measuranents of antibody-mediated toxin loss. The hypothesis that embryonic AChR may constitute the autoimmunogen in MG vas investigated by comparing the interaction of human foetal AChR with BGT and anti-(AChR) antibodies against that established for adult human AChR. Tissue sections and teased muscle fibres fron human adult and foetal muscle were compared immunohistochemically. Detergent extracts of adult and foetal AChRs were canpared in their interaction with radiolabelled BGT by kinetic measurements involving determination of association, dissociation and equilibrium binding constants. AChR was isolated and partially purified frcm human adult and foetal muscle, and their binding to anti-(AChR) antibodies in myasthenic sera and IgG were compared. No significant difference was observed between the binding characteristics of the two receptor types, indicating the absence (at least in 14 - 22 week old foetuses) of ligand binding or antigenic sites unique to foetal AChR.
Date of Award1985
Original languageEnglish
Awarding Institution
  • University of Bath

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