Effect of sera from myasthenia gravis patients on acetylcholine receptors in myotube cultures

Peter Hudgson, Mildred W. McAdams, Margaret A Pericak-Vance, Annette M. Edwards, Allen D. Roses

Research output: Contribution to journalArticle

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Abstract

Accelerated degradation of acetylcholine receptor (AChR) by antibody has been implicated in the loss of receptor sites in myasthenia gravis (MG). Our clinical and experimental data question the relevance of junctional AChR turnover in in vitro systems to the destruction of junctional human AChR sites in vivo. During the past 4 years, we have treated MG by early thymectomy, without employing other treatment modalities when possible, particularly anticholinesterase drugs and corticosteroids. Serial AChR antibody titers were determined before (n = 93) and after (n = 12) thymectomy. There was no significant difference in AChR antibody titer in the pre- versus post-thymectomy sera (P > 0.1), while all patients improved clinically. The residual fraction of AChRs in pre-thymectomy MG patients were significantly different (P < 0.001) from control values. Linear regression analysis of loge AChR destruction on loge AChR antibody level in pre-thymectomy patients was highly significant (P ≪ 0.01), with r2 = 0.44, thus indicating that a large portion of the variation of AChR destruction can be accounted for by the AChR antibody level. The residual fraction of AChRs in pre- and post-thymectomy sera were not significantly different from one another (P > 0.1), despite clinical improvement in all patients. Although there is a significant relationship between antibody titer and decreased residual fraction of AChRs in tissue culture, the relationship between these in vitro measurements and the clinical state of the patients is questionable. All our patients improved clinically post-thymectomy but their sera showed no significant difference in ability to decrease residual extrajunctional myotube AChRs. We suggest that the myotube AChR data reflect primarily an in vitro phenomenon and may not be the principal mechanism of AChR destruction in human MG.

Original languageEnglish
Pages (from-to)37-45
Number of pages9
JournalJournal of the Neurological Sciences
Volume59
Issue number1
DOIs
StatePublished - Jan 1 1983
Externally publishedYes

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Myasthenia Gravis
Skeletal Muscle Fibers
Cholinergic Receptors
Thymectomy
Serum
Antibodies
Cholinesterase Inhibitors
Adrenal Cortex Hormones
In Vitro Techniques

ASJC Scopus subject areas

  • Aging
  • Clinical Neurology
  • Surgery
  • Neuroscience(all)
  • Developmental Neuroscience
  • Neurology

Cite this

Effect of sera from myasthenia gravis patients on acetylcholine receptors in myotube cultures. / Hudgson, Peter; McAdams, Mildred W.; Pericak-Vance, Margaret A; Edwards, Annette M.; Roses, Allen D.

In: Journal of the Neurological Sciences, Vol. 59, No. 1, 01.01.1983, p. 37-45.

Research output: Contribution to journalArticle

Hudgson, Peter ; McAdams, Mildred W. ; Pericak-Vance, Margaret A ; Edwards, Annette M. ; Roses, Allen D. / Effect of sera from myasthenia gravis patients on acetylcholine receptors in myotube cultures. In: Journal of the Neurological Sciences. 1983 ; Vol. 59, No. 1. pp. 37-45.
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abstract = "Accelerated degradation of acetylcholine receptor (AChR) by antibody has been implicated in the loss of receptor sites in myasthenia gravis (MG). Our clinical and experimental data question the relevance of junctional AChR turnover in in vitro systems to the destruction of junctional human AChR sites in vivo. During the past 4 years, we have treated MG by early thymectomy, without employing other treatment modalities when possible, particularly anticholinesterase drugs and corticosteroids. Serial AChR antibody titers were determined before (n = 93) and after (n = 12) thymectomy. There was no significant difference in AChR antibody titer in the pre- versus post-thymectomy sera (P > 0.1), while all patients improved clinically. The residual fraction of AChRs in pre-thymectomy MG patients were significantly different (P < 0.001) from control values. Linear regression analysis of loge AChR destruction on loge AChR antibody level in pre-thymectomy patients was highly significant (P ≪ 0.01), with r2 = 0.44, thus indicating that a large portion of the variation of AChR destruction can be accounted for by the AChR antibody level. The residual fraction of AChRs in pre- and post-thymectomy sera were not significantly different from one another (P > 0.1), despite clinical improvement in all patients. Although there is a significant relationship between antibody titer and decreased residual fraction of AChRs in tissue culture, the relationship between these in vitro measurements and the clinical state of the patients is questionable. All our patients improved clinically post-thymectomy but their sera showed no significant difference in ability to decrease residual extrajunctional myotube AChRs. We suggest that the myotube AChR data reflect primarily an in vitro phenomenon and may not be the principal mechanism of AChR destruction in human MG.",
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