Autoantigens associated with dermatomyositis are expressed in regenerating muscle cells (brown).

Antitumor T cells may confuse regenerating muscle cells for their intended targets and attack them, according to new data from Casciola-Rosen et al. (page 591). This unsolicited attack may be the trigger for a self-perpetuating autoimmune muscle disease.Many proteins that are targeted in tissue-specific autoimmune diseases are expressed throughout the body. In most cases, the mechanisms that preferentially guide the autoreactive cells to the target tissue are not understood. An autoimmune muscle disease known as dermatomyositis is a good example. The helicase protein Mi-2 has been associated with dermatomyositis, but its expression in muscle and its function in the pathology of disease had never been explored.

Casciola-Rosen and colleagues now show that muscle cells from patients with dermatomyositis, but not those from healthy controls, expressed high levels of Mi-2 and other myositis autoantigens. In diseased muscle, autoantigens had a distinct pattern of expression—they were found only in immature regenerating muscle cells. The expression of the target antigen in regenerating muscle cells of patients suggested to the authors that it may be the effort of the damaged muscle to repair itself, and the resulting expression of the target antigen, that perpetuates the disease.

But how does this destructive cycle of muscle attack get activated in the first place? The authors found one possible explanation when they looked at tumors that are frequently associated with dermatomyositis. Similar to the situation in diseased muscle cells, they found that Mi-2 levels were elevated in tumor tissues but not in normal tissues. They suggest that an antitumor T cell response is generated against Mi-2 and other dermatomyositis-associated antigens. In the unlucky event that a nonspecific muscle injury occurs at the same time, these tumor-specific T cells might cross-react with newly growing muscle cells and trigger the self-perpetuating autoimmunity.