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

Abstract

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.

Keywords: Immunology; Macrophages; Myonuclei; Myopathies; Satellite cells.

Fig. 1

Relative fibre size distribution in type 1 and type fibres. Blue bars represent type 1 fibres. Orange bars represent type 2

Fig. 2

Illustrations of muscle biopsy findings from patients with sporadic inclusion body myositis (sIBM) A Type 1 fibres (black) were observed to be larger in size than type 2 fibres (grey). B The number of centrally placed myonuclei (red arrows) was higher in type 2 than in type 1 fibres. C The number of satellite cells (red arrows) was higher in association to type 2 fibres than to type 1 fibres. D M1 (red arrows) and M2 (green arrows) macrophages were observed to group into clusters in the vicinity of small type 2 fibres. A Green = laminin, Grey = MHC fast. B Green = laminin, Grey = MHC fast, blue = DAPI. C Green = laminin, Grey = MHC fast, blue = DAPI, red = pax7. Grey = MHC fast, blue = DAPI, yellow = CD206, red = CD68