A schematic figure of muscle tissue from myositis patients with or without inflammatory infiltrates. (1) Early in the disease, before any signs of mononuclear cell infiltrates in the muscle tissue, patients have been found to express autoantibodies (even before the development of myositis), capillaries often having the appearance of high endothelial venules (HEVs) and an expression of adhesion molecules, interleukin-1-alpha (IL-1α) and/or chemokines, major histocompatibility complex (MHC) class I on muscle fibres, and a decreased number of capillaries together with an increased expression of vascular endothelium growth factor (VEGF) on muscle fibres and in sera, suggestive of tissue hypoxia. Additionally, an increased number of fibres expressing high-mobility box chromosomal protein 1 (HMGB1) has been demonstrated early in the disease, and HMGB1 can induce MHC class I on muscle fibres. (2) All of these findings can also be found when inflammatory cell infiltrates are present. However, in these tissues, an increased production of a range of proinflammatory cytokines from mononuclear cells is also found. Moreover, non-necrotic fibres can be surrounded and sometimes invaded by cytotoxic T cells. These different pathogenic expressions from both immune and nonimmune reactions may all lead to muscle impairment. ER, endoplasmic reticulum; ICAM, intercellular adhesion molecule; IFN-α, interferon-alpha; PDC, plasmacytoid dendritic cell; VCAM, vascular cell adhesion molecule. Partly adapted from Servier Medical Art.