Signaling Pathways in Lupus
Systemic lupus erythematosus (lupus) is an autoimmune disease that can result in such devastating outcomes as renal failure and death. Treatment strategies for severe lupus rely heavily on medications that are relatively non-specific and carry a heavy burden of morbid side effects. In order to generate more targeted therapies, a more refined understanding of disease progression is needed.
It has been suspected for decades that B cells must play a critical role in disease. Indeed, human and mouse genetic and biochemical studies suggest that lupus is characterized by B cells with abnormal antigen receptor signaling. (An antigen is any substance that causes the immune system to produce antibodies against it.) Most recently, novel biologic therapies targeting B cells have been approved for lupus patients. Yet the mechanisms by which abnormal signaling through the B cell antigen receptor (BCR) produces systemic autoimmune disease remain ill-defined.
Dr. Zikherman’s study using mice will define the biochemical and cellular mechanisms involved to show how abnormal BCR signaling drives lupus progression in humans. The results may suggest more effective targets for treatment.