Muscle Disease Unit

National Institute Of Arthritis And Musculoskeletal And Skin Diseases

Investigators

Linked publications, trials & patents

Abstract

During the last year, we completed numerous clinical projects involving myositis patients. A selection of published findings included the following: (a) We demonstrated that dermatomyositis patients with anti-Mi2 autoantibodies have a unique transcriptomic signature characterized by the over-expression of genes whose transcription is known to be repressed by Mi2 protein. Along with data showing that immunoglobulin is deposited in the nuclei of dermatomyositis patients with anti-Mi2 autoantibodies, this study suggested that anti-Mi2 autoantibodies may have a direct pathogenic role in this type of autoantibody-defined dermatomyositis. (b) We participated in a clinical trial demonstrating that a C5 complement inhibitor, zilucoplan, is not effective in treating patients with immune-mediated necrotizing myopathy. Importantly, this study revealed that complement deposition on muscle fibers in these patients is unlikely to play an important pathogenic role in this type of myositis. (c) We studied the clinical features, muscle biopsy transcriptomic profiles, and muscle biopsy histology of patients with myositis triggered by immune checkpoint inhibitors. This revealed that three distinct types of myositis can be triggered by this class of drugs. Importantly, we identified histologic and transcriptomic features that identify the group of patients at risk for developing myocarditis. These patients may require more aggressive treatments than the others. (d) We studied the clinical features of a large cohort of patients with inclusion body myositis. Importantly, we found that female patients and Black patients have unique clinical presentations compared to those seen in white males. These findings will need to be accounted for in the design of clinical trials for patients with this form of muscle disease.