INCREASED GENE-EXPRESSION OF ACETYLCHOLINE-RECEPTOR AND MYOGENIC FACTORS IN PASSIVELY TRANSFERRED EXPERIMENTAL AUTOIMMUNE MYASTHENIA-GRAVIS

The passive transfer of myasthenia gravis by injection of mAb against muscle acetylcholine receptor (AChR) alpha-subunit, results in increas ed expression of AChR subunit genes, mainly at synaptic regions. The g ene expression of AChR and of other muscle-specific proteins is regula ted in a similar manner in passively transferred experimental autoimmu ne myasthenia gravis (EAMG) and in AChR-induced EAMG. Administration o f AChR-specific mAb leads to a significant reduction in muscle AChR co ntent and to an elevation in the mRNA levels corresponding to the adul t, synaptic type of the receptor, as shown by Northern blot and in sit u hybridization analyses. The mRNA levels of the myogenic factors myog enin and MRF4 are also increased moderately, whereas MyoD transcript l evels remain unchanged. Thus, passive transfer of EAMG by mAb directed to defined epitopes of AChR alpha-subunit provides a suitable model f or analyzing and following the cascade of molecular events triggered b y anti-AChR immunopathologic antibodies and may shed light on the regu latory mechanisms underlying the human disease as well.