title: Comparison of muscle ultrastructure in myasthenia gravis with anti-MuSK and anti-AChR antibodies.
abstract: Patients with myasthenia gravis (MG) with antibodies to muscle-specific receptor tyrosine kinase (MuSK) differ from acetylcholine receptor (AChR)-positive MG patients, as they frequently present with severe oculobulbar muscle weakness or with neck, shoulder, and respiratory muscle involvement. The neuromuscular junction (NMJ) has been confirmed to be the main target of both AChR- and MuSK-MG. However, histopathological investigation disclosed that muscle fiber atrophy was prevalent in AChR-MG, whereas mild myopathic changes and mitochondrial abnormalities were more frequently observed in MuSK-MG. As the pathogenetic mechanism in MuSK-MG remains unclear, this study investigated the submicroscopic pattern of muscle histopathology to establish a possible correlation between clinical involvement and subcellular morphological findings. Muscle biopsies from seven MuSK-MG patients and from seven patients with AChR-MG were analyzed by transmission electron microscopy. Myopathic and mitochondrial abnormalities were more prominent in MuSK-MG and show giant, swollen, and degenerated mitochondria with fragmented cristae. The most common changes in AChR-MG muscles were fiber atrophy, myofibrillar disarray, and Z-line streaming, consistent with mild neurogenic abnormalities. A different pathogenetic mechanism is emerging in MuSK-MG compared to AChR-MG. Mitochondrial abnormalities seem to be more prominent in MuSK-MG, whereas neurogenic atrophy is observed in AChR-MG.
authors.affiliation: Clinical Department of Radiological Histopathological Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy. giovanna.cenacchi@unibo.it
authors.forename: Giovanna
authors.initials: G
authors.lastname: Cenacchi
authors.forename: Valentina
authors.initials: V
authors.lastname: Papa
authors.forename: Papa
authors.initials: P
authors.lastname: Valentina
authors.forename: Marina
authors.initials: M
authors.lastname: Fanin
authors.forename: Fanin
authors.initials: F
authors.lastname: Marina
authors.forename: Elena
authors.initials: E
authors.lastname: Pegoraro
authors.forename: Pegoraro
authors.initials: P
authors.lastname: Elena
authors.forename: Corrado
authors.initials: C
authors.lastname: Angelini
authors.forename: Angelini
authors.initials: A
authors.lastname: Corrado
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D005260:Female; D006801:Humans; D008297:Male; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D008928:Mitochondria / Q000648:ultrastructure; D018482:Muscle, Skeletal / Q000648:ultrastructure*; D009157:Myasthenia Gravis / Q000276:immunology* / Q000473:pathology*; D009469:Neuromuscular Junction / Q000276:immunology / Q000473:pathology; D020794:Receptor Protein-Tyrosine Kinases / Q000276:immunology; D011950:Receptors, Cholinergic / Q000276:immunology; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D011950:Receptors, Cholinergic; C095714:MUSK protein, human; D020794:Receptor Protein-Tyrosine Kinases