Muscle histopathology in myasthenia gravis with antibodies against MuSK and AChR

Abstract

Aims: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.

Anti-MuSK Antibody-positive Myasthenia Gravis Mimicking Amyotrophic Lateral Sclerosis

“…Complement component 3 (C3) staining using peroxidase-labeled anti-C3 antibodies (Figure E) and immunoglobulin G (IgG) staining using peroxidase-labeled Protein A ( Figure F) revealed an absence of immune complex depositions (C3 and IgG) at the motor end-plates. These findings were consistent with the histopathological characteristics of MuSK-MG (8,9). According to the abovementioned findings, a diagnosis of MuSK-MG was established.…”

Muscle satellite cells are functionally impaired in myasthenia gravis: consequences on muscle regeneration

“…Moreover, and as we mentioned above, Maurer et al have demonstrated that IL-6 expression, was increased in myasthenic muscles of mice [42] inducing a reduction of Akt phosphorylation and activity. Furthermore, several studies have shown that muscles of MG patients displayed muscle atrophy especially in type II fibres [41,80].…”

“…The mechanisms of action of anti-AChR antibodies at the NMJ involve complement-dependent lysis of the post-synaptic membrane, receptor internalisation as well as direct interference with binding of acetylcholine to AChR [20,31]. These alterations impair the neuromuscular transmission of the signal [57,67] and thus could affect the function of the skeletal muscle fibres [41,44]. Few studies describe the effects of the anti-AChR antibodies on muscle physiology and biology.…”

Myasthenia Gravis with Anti-MuSK Antibodies: Clinical Features and Histopathological Changes

“…The ultrastructured study of biopsy from MuSK-positive patients [27] confirmed the pattern of severe myopathic changes, such as swollen mithochondria, myofibrillar loss, and sarcoplasmic reticulum lipid vesicles associated with enlarged mithocondria with electronlucent matrix and fragmented cristae [28]. Mitochondria are aggregated both in the subsarcolemmal and intermyofibrillar areas (Figure 3), adjacent to normal mitochondria.…”

“…In the past no study was done to study electron microscopy or histopathology of MuSK positive biopsies. In our study [27], we analysed muscle biopsy of 13 myasthenic patients (8 women and 5 men), whose diagnosis was based on standard criteria. Seven patients were positive for AChR-Ab (serum AChRAb > 0.25 nmol/l) and six positive for MuSK-Ab and negative for AChR-Ab.…”