The limitations associated with the different approaches into the pathogenesis of the IIM have resulted in incomplete knowledge of disease mechanisms in myositis. In most research, in which muscle tissue was used to study the different aspects of disease, biopsies with inflammatory infiltrates have been selected. Although inflammatory cell infiltrates are a characteristic feature of myositis, selecting patients with inflammatory cell infiltrates for investigations naturally introduces a selection bias. Only a few studies have been published on patients without inflammatory infiltrates but with muscle weakness, and few studies have included follow-up biopsies after different therapies. The heterogeneity of the population of patients with myositis is another limitation of the studies of pathogenic mechanisms. Although most studies classify patients according to the Bohan and Peter criteria [118, 119], some studies used histopathologic criteria [6], and only a few studies included characterization with myositis-specific autoantibodies. Because myositis-specific autoantibodies are often associated with certain clinical profiles, classification according to autoantibody profiles could be important to define differences in the pathogenesis of different phenotypes [3]. From available data on pathogenic mechanisms it is evident that cellular and humoral immune responses are involved in disease mechanisms of myositis, but whether there is a muscle-specific immune response cannot be answered by current studies. It is likely that other mechanisms are important for development of muscle weakness, including metabolic disturbances, and muscle weakness could be caused by different mechanisms in different IIM subsets or in patients in different phases of the disease. There could be early changes, which reversibly affect the metabolism, and later, irreversible changes, that could be dependent on muscle fiber damage and replacement of muscle tissue by connective tissue and fat. Current findings suggest that cytokines, which are produced in muscle tissue from different cell sources including inflammatory cells, endothelial cells, and muscle fibers, could affect muscle function. Careful follow-up studies, including the effect of therapies targeting different molecules on molecular expression in muscle tissue, are likely to increase our knowledge on disease mechanisms. A better understanding of which molecules and mechanisms affect muscle function is likely to lead to improved, less toxic therapies in patients with myositis. Many possible target molecules for blocking therapies, especially the proinflammatory cytokines IL-1 and TNF-alpha, have been identified and should be studied in appropriate clinical settings given the currently poor outcomes of many patients with IIM.
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