PROSPECTS FOR ANTI-B-CELL THERAPY IN IMMUNO-INFLAMMATORY RHEUMATIC DISEASES

Abstract

Impaired B-cell immunological tolerance plays a central role in the pathogenesis of immuno-inflammatory rheumatic diseases (IIRD). B-cells link innate and acquired immunity: they express Toll-like receptors that respond to danger signals; act as antigen-presenting cells; induce an antigen-specific immune response; determine the development of immunological memory; and synthesize a wide range of cytokines that regulate (stimulate or suppress) an immune response and inflammation. In IIRD, there are metabolic and B-cellular signaling disturbances that lead to defects in B-regulatory, T-regulatory, follicular T-helper, and dendritic cells. B-cells synthesize organ-nonspecific and organspecific autoantibodies that are biomarkers for autoimmune diseases and play an important role in their immunopathogenesis. Anti-B-cell therapy that causes B-cell depletion in blood and target organs is effective in a wide range of IIRD. Its efficiency is determined by various mechanisms, such as suppression of pathogenic autoantibody synthesis; modulation of the function of B-cells (antigen presentation, cytokine synthesis, and costimulation), T-lymphocytes and dendritic cells. Further study of a strategy for targeted anti-B-cell therapy, mechanisms of action, and new targets is important for the progress of modern rheumatology to improve the treatment strategy of IIRD.

Keywords

• immuno-inflammatory rheumatis diseases
• b-cells
• rituximab
• belimumab
• biosimilars
• acellbia