Victoria Werth, MD, University of Pennsylvania

"Immunologic Actions of Glycosaminoglycans in Cutaneous Lupus"

2008 Novel Pilot Projects Program

Skin lupus can be very disfiguring, and yet the cause of the inflammation leading to redness and scarring is poorly understood. The immune system is set up to respond to various insults, such as bacteria, and sugars on bacteria can trigger immune reactions as part of a normal response to infection. Recently, it has become clear that there are naturally occurring sugars in the skin that can be altered, and these can activate the immune system. One of these sugars, hyaluronic acid, accumulates in the skin in patients with many forms of skin lupus. This hyaluronic acid is split into small fragments by ultraviolet light. It has been shown that this fragmented hyaluronic acid can bind to receptors on the inflammatory cells in the skin, thus activating the cells and increasing the inflammation seen in the skin in lupus. There are also other sugars that are increased in the skin of patients with skin lupus, particularly in discoid lupus, and these have just recently been characterized by our immunostaining studies. Their role in lupus is completely unknown. Recent scientific developments now permit better and more specific studies about the exact reason for the increased sugars seen in the skin, as well as the role of these sugars in the inflammatory cascade of skin lupus. It is likely that they represent a very early trigger of skin disease.