Immune System Cell May Shed Light on IBM

Recent findings by researchers at Harvard Medical School, Brigham and Women’s Hospital, and Children’s Hospital, all in Boston, have identified a type of immune system cell previously undetected in the biopsy samples of people with inclusion-body myositis (IBM).

MDA grantee Steven A. Greenberg at Harvard and Brigham and Women’s, and colleagues, who published their findings in the January issue of Muscle & Nerve, say the results suggest new hypotheses about IBM, as well as new potential treatment possibilities.

The cells, called dendritic cells, haven’t been previously reported in IBM muscle samples, because their identification requires looking at muscle specimens using specific markers, Greenberg says. Previous studies have used a more general type of marker and have misidentified many of the dendritic cells as T-cells, a better known immune system cell.

“Until the last decade, the study of dendritic cells has been relatively neglected in immunology and particularly in autoimmune disease,” Greenberg says, referring to diseases in which the body’s immune system mistakenly attacks its own tissue. Polymyositis (PM) and dermatomyositis (DM), in which dendritic cells have previously been noted, have long been classified as autoimmune disorders. Experts have disagreed about how to classify IBM, although most believe the immune system is involved in some way.

“These [dendritic] cells are now recognized as central to the initiation and development of specific immune responses,” Greenberg says. One type, myeloid dendritic cells, is particularly abundant in IBM muscle tissue.

“Myeloid dendritic cells activate other immune system cells, particularly T-cells that are believed to be a major cause of muscle damage in IBM and polymyositis. Their presence in IBM and PM muscle provides a means by which these T-cells become activated and attack muscle.”

Greenberg says new therapies for autoimmune diseases aimed at disrupting the function of dendritic cells and their interaction with T-cells could be considered for future trials in myositis, given these findings. He notes that two drugs -- abatacept (Orencia) and efalizumab (Raptiva), both of which interfere with dendritic cell-T-cell interactions -- are already approved by the Food and Drug Administration for other conditions.