acetylcholine-receptor-alpha-subunit-(125-148) and Myasthenia-Gravis

To investigate the role of the acetylcholine receptor (AchR) in the pathogenesis of paraneoplastic Myasthenia gravis (MG), we screened a cDNA library of a MG-associated thymoma with a DNA oligonucleotide coding for aa 371-378, i.e. for part of the very immunogenic cytoplasmatic epitope (VICE-alpha, aa 373-380) of the human AChR alpha-subunit. We isolated two cDNA clones. Analysis of these clones has identified an open reading frame of 1371 bp, coding for the AChR alpha-subunit. No point mutation, insertion or deletion could be detected. Since the thymoma did not contain thymic myoid cells, which normally express AChR, the origin of the AChR transcripts must be the tumor cells itself. These findings confirm former results, where AChR alpha-subunit sequences from MG-thymomas were amplified by PCR.

Topics: Base Sequence; Blotting, Northern; Cloning, Molecular; DNA, Complementary; Humans; Immunohistochemistry; Molecular Sequence Data; Myasthenia Gravis; Peptide Fragments; Receptors, Nicotinic; RNA, Messenger; Thymoma

Each of 10 rats inoculated with a synthetic peptide comprising residues 125-147 (without a disulfide bond) of human acetylcholine receptor (AChR) alpha-subunit (H alpha) had deposits of IgG and C3 (immune complexes) and showed morphological changes in the fine structure at the motor end-plates 5 weeks after a single immunization. Antibody to the H alpha peptides was elevated 1 week after immunization, but, antibody levels to solubilized human or rat AChR were very low in 8 of the 10 rats. These results suggest that the immune response to peptide H alpha is the myasthenogenic site, which induces morphological change at the end-plates.

Topics: Animals; Epitopes; Female; Immunization; Microscopy, Electron; Motor Endplate; Myasthenia Gravis; Peptide Fragments; Rats; Rats, Inbred Lew; Receptors, Cholinergic; Receptors, Nicotinic

We measured the amount of antibodies to a synthetic peptide that corresponds to the alpha-subunit residues Lys125-Thr148 of human acetylcholine receptor (AChR) in myasthenic sera. We detected anti-peptide antibodies in 52% (89/171) of the patients with myasthenia gravis (MG), but none in any of the healthy controls. Anti-peptide antibodies should provide a valuable immunologic parameter for the clinical evaluation of MG, but no apparent correlation was observed between the titers of anti-peptide and anti-AChR antibodies.

Topics: Autoantibodies; Humans; Myasthenia Gravis; Peptide Fragments; Receptors, Nicotinic; Thymoma; Thymus Neoplasms