Evidence against acetylcholine receptor having a main immunogenic region as target for autoantibodies in myasthenia gravis

Vanda A. Lennon, Guy E. Griesmann

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

We investigated specificities of acetylcholine receptor (AChR) antibodies in 100 seropositive patienta with myasthenia gravis (MG). Antibodies in 74 of these sera were inhibited by more than 50% from binding to human muscle AChR by a rat monoclonal antibody (mAb) of “main immunogenic region” (MIR) specificity. The mAb inhibition was not explainable by epitope competition because (1) the mAb was reactive with both Torpedo and human AChR, but antibodies in 85 of the MG sera did not bind to Torpedo AChR, and (2) the mAb blocked binding of rat anti-peptide antibodies to an a subunit region of the human AChR unrelated antigenically to the designated MIR region. Individual patients’ sera had evidence of extensive antibody heterogeneity and revealed interspecies polymorphism in AChR antigenicity, near and remote from the neurotransmitter-binding region. The data challenge the concept that a MIR of the AChR is the principal stimulus for antibody production in MG, and emphasize a potential pitfall in assuming seronegativity in MG on the basis of a single assay system.

Original languageEnglish (US)
Pages (from-to)1069-1076
Number of pages8
JournalNeurology
Volume39
Issue number8
StatePublished - Aug 1989

ASJC Scopus subject areas

  • Clinical Neurology

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