Rituximab

Rituximab is a monoclonal antibody that targets CD20, an antigen expressed on the surface of pre-B and mature B-lymphocytes. About 85% of non-Hodgkin’s lymphoma (NHL) cases are B-cell lymphomas, characterized by the high expression of CD19, CD20 and CD22 cell surface antigens. CD20 is involved in cell cycle regulation, apoptosis and calcium signaling. By targeting CD20, rituximab promotes cell lysis while sparing hematopoietic and plasma cells without this surface antigen. It has been suggested that cell lysis mechanisms triggered by rituximab include complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC). Rituximab is part of the immunoglobulin G1 (IgG1) subclass of antibodies, and is formed by a murine variable region (Fab region) and a human constant region (Fc region). The Fab region gives rituximab its specificity for CD20, while the Fc region interacts with cell surface receptors to activate the immune system, leading to the depletion of circulating B lymphocytes.

In regards to the mechanism of action in rheumatoid arthritis (RA), B-cells are thought to play a role in the pathogenesis of RA and the associated condition of chronic synovitis. B-cells may act at various sites in the autoimmune/inflammatory process through the production of rheumatoid factor (RF) and other autoantibodies, antigen presentation, T-cell activation, and the production of proinflammatory cytokines. The administration of rituximab in this condition has resulted in significant clinical and symptomatic improvements. Rituximab is also indicated for the treatment of granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), two conditions characterized by the presence of circulating antineutrophil cytoplasmic antibodies and increased B-cell activity. It has been suggested that rituximab depletes CD20+ B-cells at a higher rate in GPA and MPA patients with high levels of Fc receptor-like 5 (FCRL5).