Monoclonal antibodies and fusion proteins and their complications: Targeting B cells in autoimmune diseases

The immune system consists of a complex array of immunocompetent cells and inflammatory mediators that exist in complex networks. These components interact through cascades and feedback circuits, maintaining physiologic inflammation and immunosurveillance. In various autoimmune conditions, a foreign or auto-antigen may upset this fine balance, leading to dysregulated immunity, persistent inflammation, and ultimately pathologic sequelae. In recent years, there has been tremendous progress delineating the specific components of the immune system that contribute to normal immunity and specific disease states. With this greater understanding of pathogenesis coupled with advances in biotechnology, many immunomodulatory agents, commonly called biologic agents, have been introduced. The 2 most common classes of biologic agents are monoclonal antibodies and fusion proteins. These agents can inhibit targets with exquisite specificity to optimize outcomes and minimize toxicity. B cells contribute significantly to the initiation and perpetuation of the immune responses. B cells not only can produce potentially pathologic autoantibodies and proinflammatory cytokines but also can present antigens to T cells and provide costimulatory signals essential for T-cell activation, clonal expansion, and effector function. This review focuses on biologic agents targeting B cells in the treatment of rheumatoid arthritis and systemic lupus erythematosus.