The Clinical Research Component, an integral part of the proposed Autoimmunity Center of Excellence, shares with the Basic Research Component an overall goal of advancing the treatment of autoimmune disease through B cell targeted approaches. Dr. E. William St.Clair, the Principal Investigator of the proposed Center, will direct the Clinical Research Component. Duke University Medical Center has a wealth of superb clinical investigators and resources to support in excellence the development and implementation of clinical trials. To meet the requirements set forth in the Request for Applications, we have assembled a talented group of experienced clinical investigators with expertise across a broad spectrum of autoimmune disease. Each of the investigators is a clinical expert in the conduct of clinical trials, with access to the relevant patient populations. These investigators include Drs. St.Clair, Sandy, Pisetsky, Hall, Schanberg, Ortel, Onken, and Sanders, representing expertise in rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), autoimmune blistering diseases, juvenile arthritis and pediatric SLE, anti-phospholipid antibody syndrome, imflammatory bowel disease, and myasthenia gravis. All of these investigators have documented their commitment to support the research activities within the Center. We propose two clinical trials on the cutting-edge of therapeutics for autoimmune disease. One of the trials will investigate the effects of a novel anti-CD22 monoclonal antibody (mAb) in RA. CD22 is expressed on the surface of mature B cells and acts as both a positive and negative regulator of B celt function. Mechanistic studies will determine the extent to which this intervention changes the phenotype and signaling properties of B cells, paralleling the mouse studies ofanti-CD20 and anti-CD22 mAb described in Basic Research Project 1. The other trial will examine the clinical benefits of infliximab therapy (chimeric anti-TNF mAb) for pemphigus vulgaris. Pemphigus vulgaris is a rare, autoimmune blistering disease in which excessive TNFalpha production and antibodies to desmoglein-3 play important roles in the pathogenesis of the skin lesions. The mechanistic studies for this trial will determine if the neutralization of TNFalpha interferes with the mobilization of immature B cells from the bone marrow and selection of the autoreactive B cell repertoire, a hypothesis also addressed experimentally in Basic Research Project 2.