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X-linked vacuolated myopathy: complement membrane attack complex on surface membrane of injured muscle fibers
M Villanova1, J P Louboutin, D Chateau
1INSERM U. 153, Paris, France.
Abstract:
We describe a probable recessive X-linked myopathy characterized by the presence of vacuolated muscle fibers. Four males and their shared maternal grandfather were affected. Clinical characteristics include juvenile onset, very slow progression, and predominant proximal muscle involvement. The clinical picture and the morphological findings are compared with those previously described in a family. By immunofluorescence, all histologically abnormal muscle fibers, in particular those vacuolated, showed a strong deposition of the complement C5b-9 membrane attack complex over the whole muscle fiber surface. Weak immunostaining for membrane attack complex was also found in endomysial capillaries and perimysial vessel walls. Muscle fibers showed sarcolemmal immunolabeling with anti-major histocompatibility complex I, which was also present on the margins of many vacuoles. All vacuoles were stained by antidystrophin antibody, which colocalized in most of them with antilaminin immunostaining. Taken together, these results suggest that the deposition of membrane attack complex on the damaged cell surface membrane could be important in the pathogenesis of this muscle disorder, and that the membrane-bounded vacuoles could be a consequence of sarcolemmal invagination.
Insights
This study identifies a rare X-linked myopathy with vacuolated muscle fibers. Complement C5b-9 membrane attack complex deposition on damaged muscle membranes may drive this progressive neuromuscular disorder.
Area of Science:
- Neurology
- Genetics
- Cell Biology
Background:
- X-linked myopathies are a group of genetic disorders affecting muscle function.
- Vacuolated muscle fibers are a distinctive morphological feature observed in certain myopathies.
- Understanding the underlying mechanisms of rare neuromuscular disorders is crucial for developing targeted therapies.
Purpose of the Study:
- To characterize a probable recessive X-linked myopathy with vacuolated muscle fibers.
- To investigate the role of complement system activation in the pathogenesis of this myopathy.
- To explore the relationship between sarcolemmal abnormalities, vacuole formation, and disease progression.
Main Methods:
- Histological examination of muscle biopsies.
- Immunofluorescence staining for complement C5b-9 membrane attack complex, major histocompatibility complex I, dystrophin, and laminin.
- Clinical assessment of affected individuals, including disease onset, progression, and muscle involvement.
Main Results:
- A probable recessive X-linked myopathy was identified in four males and their maternal grandfather.
- Affected muscle fibers exhibited significant deposition of complement C5b-9 membrane attack complex on their surface.
- Vacuoles within muscle fibers stained positive for dystrophin and laminin, suggesting sarcolemmal origin.
Conclusions:
- Deposition of the complement C5b-9 membrane attack complex on damaged muscle cell membranes appears to be a key factor in the pathogenesis of this myopathy.
- Membrane-bounded vacuoles likely result from sarcolemmal invaginations, contributing to the disease phenotype.
- This research sheds light on the molecular mechanisms of a rare X-linked neuromuscular disorder.