Project 452946

Systemic lupus erythematosus (SLE) is an autoimmune condition where the body's immune system attacks its own cells and tissues. There is no cure yet and available medications can only help to control symptoms. The patient's hope resides in scientific research, investigating the cause of lupus and helping in developing therapies and cure. Causes of this disease remain largely unknown but many factors have been shown to be involved at this level. Recent research work by several groups including ours has demonstrated that CD154, an immunological molecule expressed on the surface of a type of white blood cells, is implicated in autoimmune processes including SLE. Therefore, CD154 was thought to be a good target for therapeutic intervention in these diseases, and antibodies against this molecule have been produced and utilized as therapies in studies involving animals or humans. Such therapy directed against the CD154 molecule as a whole and blocking all its activities was shown to be effective in some autoimmune disorders, however serious side effects such as blood clotting complications have been reported. To overcome these adverse events, our group wants to identify how CD154 is really involved in SLE causation and generate tools to stop only the irregular function of CD154 in SLE rather than the whole immune role of the molecule. In this matter, we have generated molecules that would act to block only certain effects of CD154 without affecting its global activities. We will assess these molecules in animals that develop lupus. Our modified CD154 molecules are expected to treat SLE without causing side effects. Thus, our studies will both expand our understanding of the role of CD154 in SLE, and will help in the design of new therapeutic strategies for treatment for the disease.