Modulation of acetylcholine receptor expression in seronegative myastheniagravis.

In a previous study, we demonstrated a compensatory mechanism for regulatin g acetylcholine receptor (AChR) gene expression in muscle biopsies from ser opositive and seronegative (SN) myasthenia gravis (MG) patients. To further characterize the AChR regulation mechanisms involved in SNMG disease, we i nvestigated the effects of MG sera on nicotinic AChR expression (at the pro tein and messenger RNA [mRNA] levels) in cultured human muscle cells. Sera from SNMG patients induced an in vitro increase in the level of nicotinic A ChR beta -subunit mRNA hut did not cause a decrease in AChR protein level. This apparent discrepancy was not due to a higher level of AChR synthesis a s demonstrated by analysis of AChR turnover. In SN patients, the increase i n beta -subunit mRNA level was followed after 48 hours by a slight increase in the amount of AChR surface protein. This regulation of nicotinic recept or expression was due to the purified IgG-containing fraction. Thus, sera f rom SNMG patients contain an immunoglobulin that induces an increase in ACh R mRNA without causing a decrease in AChR protein level, suggesting an indi rect regulatory mechanism involving another surface molecule. This model is therefore useful for defining the targets involved in the pathogenesis of SNMG disease.