Thrombospondin-1 mediates muscle damage in brachio-cervical inflammatory myopathy and systemic sclerosis
Por:
Suarez-Calvet, X, Alonso-Perez, J, Castellvi, I, Carrasco-Rozas, A, Fernandez-Simon, E, Zamora, C, Martinez-Martinez, L, Alonso-Jimenez, A, Rojas-Garcia, R, Turon, J, Querol, L, de Luna, N, Milena-Millan, A, Corominas, H, Castillo, D, Cortes-Vicente, E, Illa, I, Gallardo, E, Diaz-Manera, J
Publicada:
1 may 2020
Resumen:
Objective To describe the clinical, serologic and histologic features of a cohort of patients with brachio-cervical inflammatory myopathy (BCIM) associated with systemic sclerosis (SSc) and unravel disease-specific pathophysiologic mechanisms occurring in these patients. Methods We reviewed clinical, immunologic, muscle MRI, nailfold videocapillaroscopy, muscle biopsy, and response to treatment data from 8 patients with BCIM-SSc. We compared cytokine profiles between patients with BCIM-SSc and SSc without muscle involvement and controls. We analyzed the effect of the deregulated cytokines in vitro (fibroblasts, endothelial cells, and muscle cells) and in vivo. Results All patients with BCIM-SSc presented with muscle weakness involving cervical and proximal muscles of the upper limbs plus Raynaud syndrome, telangiectasia and/or sclerodactilia, hypotonia of the esophagus, and interstitial lung disease. Immunosuppressive treatment stopped the progression of the disease. Muscle biopsy showed pathologic changes including the presence of necrotic fibers, fibrosis, and reduced capillary number and size. Cytokines involved in inflammation, angiogenesis, and fibrosis were deregulated. Thrombospondin-1 (TSP-1), which participates in all these 3 processes, was upregulated in patients with BCIM-SSc. In vitro, TSP-1 and serum of patients with BCIM-SSc promoted proliferation and upregulation of collagen, fibronectin, and transforming growth factor beta in fibroblasts. TSP-1 disrupted vascular network, decreased muscle differentiation, and promoted hypotrophic myotubes. In vivo, TSP-1 increased fibrotic tissue and profibrotic macrophage infiltration in the muscle. Conclusions Patients with SSc may present with a clinically and pathologically distinct myopathy. A prompt and correct diagnosis has important implications for treatment. Finally, TSP-1 may participate in the pathologic changes observed in muscle.
Filiaciones:
Suarez-Calvet, X:
Hosp Santa CreuiSt Pau, Neurol Dept, Neuromuscular Dis Unit, Barcelona, Spain
Biomed Res Inst St Pau IIB St Pau, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid, Spain
Alonso-Perez, J:
Hosp Santa CreuiSt Pau, Neurol Dept, Neuromuscular Dis Unit, Barcelona, Spain
Biomed Res Inst St Pau IIB St Pau, Barcelona, Spain
Castellvi, I:
Hosp Santa Creu & Sant Pau, Rheumatol Unit, Barcelona, Spain
Carrasco-Rozas, A:
Hosp Santa CreuiSt Pau, Neurol Dept, Neuromuscular Dis Unit, Barcelona, Spain
Biomed Res Inst St Pau IIB St Pau, Barcelona, Spain
Fernandez-Simon, E:
Hosp Santa CreuiSt Pau, Neurol Dept, Neuromuscular Dis Unit, Barcelona, Spain
Biomed Res Inst St Pau IIB St Pau, Barcelona, Spain
Zamora, C:
Hosp Santa Creu & Sant Pau, Biomed Res Inst St Pau IIB St Pau, Lab Expt Immunol, Barcelona, Spain
Martinez-Martinez, L:
Hosp Santa Creu & Sant Pau, Biomed Res Inst St Pau IIB St Pau, Serv Immunol, Barcelona, Spain
Alonso-Jimenez, A:
Hosp Santa CreuiSt Pau, Neurol Dept, Neuromuscular Dis Unit, Barcelona, Spain
Biomed Res Inst St Pau IIB St Pau, Barcelona, Spain
Rojas-Garcia, R:
Hosp Santa CreuiSt Pau, Neurol Dept, Neuromuscular Dis Unit, Barcelona, Spain
Biomed Res Inst St Pau IIB St Pau, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid, Spain
Turon, J:
Hosp Santa CreuiSt Pau, Neurol Dept, Neuromuscular Dis Unit, Barcelona, Spain
Biomed Res Inst St Pau IIB St Pau, Barcelona, Spain
Querol, L:
Hosp Santa CreuiSt Pau, Neurol Dept, Neuromuscular Dis Unit, Barcelona, Spain
Biomed Res Inst St Pau IIB St Pau, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid, Spain
de Luna, N:
Hosp Santa CreuiSt Pau, Neurol Dept, Neuromuscular Dis Unit, Barcelona, Spain
Biomed Res Inst St Pau IIB St Pau, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid, Spain
Milena-Millan, A:
Hosp Santa Creu & Sant Pau, Rheumatol Unit, Barcelona, Spain
Corominas, H:
Hosp Santa Creu & Sant Pau, Rheumatol Unit, Barcelona, Spain
Castillo, D:
Hosp Santa Creu & Sant Pau, Dept Resp Med, Barcelona, Spain
Cortes-Vicente, E:
Hosp Santa CreuiSt Pau, Neurol Dept, Neuromuscular Dis Unit, Barcelona, Spain
Biomed Res Inst St Pau IIB St Pau, Barcelona, Spain
Illa, I:
Hosp Santa CreuiSt Pau, Neurol Dept, Neuromuscular Dis Unit, Barcelona, Spain
Biomed Res Inst St Pau IIB St Pau, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid, Spain
Gallardo, E:
Hosp Santa CreuiSt Pau, Neurol Dept, Neuromuscular Dis Unit, Barcelona, Spain
Biomed Res Inst St Pau IIB St Pau, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid, Spain
Diaz-Manera, J:
Hosp Santa CreuiSt Pau, Neurol Dept, Neuromuscular Dis Unit, Barcelona, Spain
Biomed Res Inst St Pau IIB St Pau, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid, Spain
Univ Newcastle, John Walton Muscular Dystrophy Res Ctr, Newcastle Upon Tyne, Tyne & Wear, England
Gold, Green Published
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