title: Modulation of acetylcholine receptor expression in seronegative myasthenia gravis.
abstract: In a previous study, we demonstrated a compensatory mechanism for regulating acetylcholine receptor (AChR) gene expression in muscle biopsies from seropositive and seronegative (SN) myasthenia gravis (MG) patients. To further characterize the AChR regulation mechanisms involved in SNMG disease, we investigated the effects of MG sera on nicotinic AChR expression (at the protein and messenger RNA [mRNA] levels) in cultured human muscle cells. Sera from SNMG patients induced an in vitro increase in the level of nicotinic AChR beta-subunit mRNA but did not cause a decrease in AChR protein level. This apparent discrepancy was not due to a higher level of AChR synthesis as demonstrated by analysis of AChR turnover. In SN patients, the increase in beta-subunit mRNA level was followed after 48 hours by a slight increase in the amount of AChR surface protein. This regulation of nicotinic receptor expression was due to the purified IgG-containing fraction. Thus, sera from SNMG patients contain an immunoglobulin that induces an increase in AChR mRNA without causing a decrease in AChR protein level, suggesting an indirect regulatory mechanism involving another surface molecule. This model is therefore useful for defining the targets involved in the pathogenesis of SNMG disease.
authors.affiliation: CNRS ESA 8078, Hôpital Marie Lannelongue, Le Plessis-Robinson, France.
authors.forename: S
authors.initials: S
authors.lastname: Poea
authors.forename: T
authors.initials: T
authors.lastname: Guyon
authors.forename: J
authors.initials: J
authors.lastname: Bidault
authors.forename: C
authors.initials: C
authors.lastname: Bruand
authors.forename: V
authors.initials: V
authors.lastname: Mouly
authors.forename: S
authors.initials: S
authors.lastname: Berrih-Aknin
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009132:Muscles / Q000276:immunology; D009157:Myasthenia Gravis / Q000097:blood* / Q000276:immunology*; D012333:RNA, Messenger / Q000097:blood / Q000276:immunology; D011950:Receptors, Cholinergic / Q000097:blood / Q000276:immunology*
chemical_list: D012333:RNA, Messenger; D011950:Receptors, Cholinergic