Muscle histopathology in myasthenia gravis with antibodies against MuSK and AChR.
OBJECTIVE
We compared myopathological features in myasthenia gravis (MG) patients with antibodies against AChR (seropositive) and muscle-specific tyrosin-kinase (MuSK). While the immunopathogenesis of seropositive MG is well known, there is a lack of pathological studies in anti-MuSK antibody-positive (MuSK+) MG.


METHODS
We analysed skeletal muscle biopsy features of 13 MG patients: 6 MuSK+ (all women) and 7 anti-AchR antibody-positive (AChR+) (2 women and 5 men). In our histopathological examination, we quantified the atrophy factor of both fibre types, and the extent of minicores, myofibrillar disarray, cytochrome c oxidase (COX)-negative fibres, mitochondrial aggregates and fibre type grouping.


RESULTS
Mean muscle fibre atrophy factor was higher in AChR+ MG than MuSK+ MG, both in type I fibres (494 vs. 210) and particularly in type II fibres (1023 vs. 300). Fibre type grouping was observed in AChR+ MG whereas COX-negative fibres were common in MuSK+ MG. Bulbar muscles were more severely affected in MuSK+ MG and the disease was more severe: the onset was usually earlier (39 years) with Myasthenia Gravis Foundation of America score III in MuSK+ MG, and score II was found in AChR+ MG (62 years).


CONCLUSIONS
Muscle biopsies of MuSK+ MG show myopathic signs with prominent mitochondrial abnormalities, whereas neurogenic features and atrophy are more frequently found in AChR+ MG. The mitochondrial impairment could explain the oculo-bulbar involvement in MuSK+ MG.
Martignago
S
S
Department of Neurosciences, University of Padova, Padova, Italy.
Fanin
M
M
Albertini
E
E
Pegoraro
E
E
Angelini
C
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000097:blood*; D003576:Electron Transport Complex IV / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria; D018485:Muscle Fibers, Skeletal / Q000473:pathology* / Q000502:physiology; D009133:Muscular Atrophy / Q000276:immunology / Q000473:pathology; D009157:Myasthenia Gravis / Q000276:immunology / Q000473:pathology*; D009246:NADH Tetrazolium Reductase / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000276:immunology*; D011950:Receptors, Cholinergic / Q000276:immunology*
D001323:Autoantibodies; D011950:Receptors, Cholinergic; D009246:NADH Tetrazolium Reductase; D003576:Electron Transport Complex IV; C095714:MUSK protein, human; D020794:Receptor Protein-Tyrosine Kinases