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Brain. 2018 Jun 1;141(6):1609-1621. doi: 10.1093/brain/awy105.

JAK inhibitor improves type I interferon induced damage: proof of concept in dermatomyositis.

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Sorbonne Université, INSERM, Association Institut de Myologie, Center of Research in Myology, UMRS 974, AP-HP, Department of Internal Medicine and Clinical Immunology, DHU I2B, Pitié-Salpêtrière Hospital, F-75013, Paris, France.
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Neuromuscular Diseases Unit, Neurology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona and Institut de Recerca Sant Pau, Barcelona, Spain.
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain.
Laboratory of Neurogenetics and Neuroinflammation, Institut National de la Santé et de la Recherche Médicale (INSERM) UMR1163 and Université Paris Descartes, Université Sorbonne Paris Cité, Institut Imagine, 75015 Paris, France.
Leibniz-Institut für Analytische Wissenschaften - ISAS - e.V, Biomedical Research Department, Tissue Omics group, Otto-Hahn-Str. 6b, 44227, Dortmund, Germany.
INSERM UMR 1223 and Laboratory of Dendritic Cell Immunobiology, Institut Pasteur, Paris, France.
Department of Neuropathology, Charité University, Berlin, Germany.
Department of Internal Medicine, Saint Joseph Hospital, Marseille, France.
Departement de Virologie, Hôpital Cochin, Paris Descartes Universités, Paris, France.
Institute of Genetic Medicine, John Walton Muscular Dystrophy Research Centre, International Centre for Life, Central Parkway, Newcastle upon Tyne, England, UK.


Dermatomyositis is an acquired auto-immune disease characterized by skin lesions and muscle-specific pathological features such as perifascicular muscle fibre atrophy and vasculopathy. Dermatomyositis patients display an upregulation of type I interferon-inducible genes in muscle fibres, endothelial cells, skin and peripheral blood. However, the effect of type I interferon on muscle tissue has not yet been determined. Our aim was to study the pathogenicity of type I interferon in vitro and to evaluate the efficacy of the type I interferon pathway blockade for therapeutic purposes. The activation of type I interferon in differentiating myoblasts abolished myotube formation with reduced myogenin expression while in differentiated myotubes, we observed a reduction in surface area and an upregulation of atrophy-associated genes. In vitro endothelial cells exposure to type I interferon disrupted vascular network organization. All the pathogenic effects observed in vitro were abolished by ruxolitinib. Finally, four refractory dermatomyositis patients were treated with ruxolitinib and improvement ensued in skin lesions, muscle weakness and a reduced serum type I interferon levels and interferon-inducbile genes scores. We propose JAK inhibition as a mechanism-based treatment for dermatomyositis, a finding that is relevant for the design of future clinical trials targeting dermatomyositis.


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