In this fiscal year, we completed numerous clinical projects involving myositis patients. These projects included: (a) Defining the nature of interferon (IFN) pathway activation in muscle tissue from patients with each type of myositis. Although prior studies had shown that dermatomyositis muscle has a prominent type I IFN signature, the nature of the type I and type II IFN signatures in muscle tissue from those with the other types of myositis had not been investigated. We published a paper showing that (i) antisynthetase syndrome patients have moderate type I IFN and high type II IFN signatures, (ii) inclusion body myositis patients have low type I and high type II IFN signatures, and (iii) immune-mediated necrotizing myopathy patients have low type I and low type II IFN signatures. These results suggest that targeting the IFN pathway could be considered for patients with inclusion body myositis or antisynthetase syndrome, but may be less likely to be effective for immune-mediated necrotizing myopathy. (b) Studying the role of autoantigen expression on the development of myositis-specific autoantibodies. Myositis patients typically produce a single type of myositis-specific autoantibody. It had been suggested that over-expression of a given myositis autoantigen causes the production of autoantibodies recognizing that protein. However, we published a study demonstrating that all myositis autoantigens are expressed at high levels in the regenerating muscle tissue of patients with each type of myositis-specific autoantibody. Thus, the over-expression of a given myositis autoantigen is unlikely to determine which autoantibodies are produced by a given myositis patient. (c) Analyzing a longitudinal cohort of adult myositis patients with anti-U1-RNP autoantibodies. Glomerulonephritis and pericarditis are exceptionally rare among patients with most types of myositis. However, this published study established that glomerulonephritis and pericarditis occurred in 25% and 40% of anti-U1-RNP-positive myositis patients. Importantly glomerulonephritis and pericarditis only occurred in those patients who were also positive for anti-Ro52 autoantibodies. This study also demonstrated that anti-U1-RNP-positive patients typically have muscle biopsies characterized by myofiber necrosis without prominent lymphocytic infiltrates. (d) In collaboration with Dr. Lisa Rider, Dr. Fred Miller, and their colleagues at NIEHS, we published a paper describing the the phenotype of pediatric myositis patients with anti-Ro52 autoantibodies. We found that children with myositis who have anti-Ro52 autoantibodies have more severe disease manifestations such as interstitial lung disease.
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