Effects of sporadic inclusion body myositis on skeletal muscle fibre type specific morphology and markers of regeneration and inflammation

Kasper Yde Jensen1,2,3, Jakob Lindberg Nielsen3, Per Aagaard3, Mikkel Jacobsen3,2, Anders Nørkær Jørgensen3,4, Rune Dueholm Bech5, Ulrik Frandsen3, Louise Pyndt Diederichsen6,1, Henrik Daa Schrøder2
1Copenhagen Research Center for Autoimmune Connective Tissue Diseases (COPEACT), Center for Rheumatology and Spine Diseases, Copenhagen University Hospital, Copenhagen, Denmark
2Department of Pathology, Department of Clinical Research, University of Southern Denmark, Odense University Hospital, Odense, Denmark
3Department of Sports Science and Clinical Biomechanics, University of Southern Denmark, Odense, Denmark
4Department of Clinical Research, University of Southern Denmark, Odense, Denmark
5Department of Orthopaedics and Traumatology, Zealand University Hospital, Koege, Denmark
6Department of Rheumatology, Odense University Hospital, Odense, Denmark

Tóm tắt

Sporadic inclusion body myositis (sIBM) is a subgroup of idiopathic inflammatory myopathies characterised by progressive muscle weakness and skeletal muscle inflammation. Quantitative data on the myofibre morphology in sIBM remains scarce. Further, no previous study has examined fibre type association of satellite cells (SC), myonuclei number, macrophages, capillaries, and myonuclear domain (MD) in sIBM patients. Muscle biopsies from sIBM patients (n = 18) obtained previously (NCT02317094) were included in the analysis for fibre type-specific myofibre cross-sectional area (mCSA), SCs, myonuclei and macrophages, myonuclear domain, and capillarisation. mCSA (p < 0.001), peripheral myonuclei (p < 0.001) and MD (p = 0.005) were higher in association with type 1 (slow-twitch) than type 2 (fast-twitch) fibres. Conversely, quiescent SCs (p < 0.001), centrally placed myonuclei (p = 0.03), M1 macrophages (p < 0.002), M2 macrophages (p = 0.013) and capillaries (p < 0.001) were higher at type 2 fibres compared to type 1 fibres. In contrast, proliferating (Pax7+/Ki67+) SCs (p = 0.68) were similarly associated with each fibre type. Type 2 myofibres of late-phase sIBM patients showed marked signs of muscle atrophy (i.e. reduced mCSA) accompanied by higher numbers of associated quiescent SCs, centrally placed myonuclei, macrophages and capillaries compared to type 1 fibres. In contrast, type 1 fibres were suffering from pathological enlargement with larger MDs as well as fewer nuclei and capillaries per area when compared with type 2 fibres. More research is needed to examine to which extent different therapeutic interventions including targeted exercise might alleviate these fibre type-specific characteristics and countermeasure their consequences in impaired functional performance.

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