Studies in sporadic inclusion body myositis

University dissertation from Stockholm : Karolinska Institutet, Department of Clinical Neuroscience

Abstract: Aims: The general aims of the present study were to increase the understanding of the disease process in s-lBM by analysing the cytoskeletal structure in muscle fibres and their regeneration potential; and also to evaluate sensory function in patients with s-IBM to test the hypothesis of an associated neurogenic component or a concomitant neuropathy in s-IBM; and to evaluate therapeutic options by analysing the effect of IVIg treatment on the muscle inflammation; and to evaluate the effect of training on muscle function and muscle inflammation. Patients: Twenty-six patients with the diagnosis of s41BM participated in these studies. The diagnosis was based on clinical symptoms and signs as well as histopathological changes in muscle biopsy, using the diagnostic criteria for s-IBM according to Griggs et al. (1995). All patients had light microscopic muscle biopsy findings with inflammatory infiltrates including invasion of non-necrotic muscle fibres and rimmed vacuoles. The diagnosis was also verified by means of electron microscopy showing cytoplasmic tubulofilaments, 15-18 run in diameter. Methods: The cytoskeleton and regeneration activity in muscle from s-IBM patients were analysed by immunohistochemical methods, as was expression of T lymphocytes, macrophages, endothelial cells, cytokines, adhesion molecules and class I and II human leukocyte antigen (HLA). Repeated muscle biopsies were performed before and after IVIg treatment and before and after physical training. Safety and benefit of training was evaluated in a 12-week home training program. Quantitative sensibility tests and electrophysiology were used to analyse the sensory function in patients with s-IBM. Results: The expression of the intermediate filament vimentin and upregulation of desmin as well as expression of the satellite cell antigen CD56, indicates an ongoing active muscle fibre regeneration in s-IBM. This is ftirther supported by the presence of neonatal myosin. Sensibility dysfunction found in s-IBM patients indicates involvement of both large myelinated and unmyelinated nerve fibres. The effect of IVIg treatment on immunological markers, including HLA class I and II expression on muscle fibres, adhesion molecules and cytokine expression in capillaries and muscle inflammation is surprisingly small when muscle biopsies taken before and after IVIg treatment are compared. The home training program was well tolerated by patients with s-IBM and gave subjective positive effects on muscle function. Conclusion: The muscle fibres in s41BM do have the ability to regenerate and there is an ongoing regeneration during the disease process, which may be a powerful compensatory phenomenon. However, it is not enough effective to overcome the disease process. IVIg treatment, which in some reports has been suggested to have a beneficial effect in s-IBM, has little effect on the presence of inflammatory cells or on the expression of cytokines and adhesion molecules in muscle tissue. Thus these results do not support the contention that IVIg treatment can be effective in s-IBM. Moderate physical training is safe for patients with s-IBM and can possibly have positive effect on muscle strength and function. Finally, the sensory dysfunctions found in this study support the notion that there is a peripheral nerve involvement in s-IBM.

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