Targeting B cells and plasma cells in autoimmune diseases: From established treatments to novel therapeutic approaches

Abstract

Autoimmune diseases are characterized by the recognition of self-antigens by the immune system, which leads to inflammation and tissue damage. B cells are directly and indirectly involved in the pathophysiology of autoimmunity, both via antigen-presentation to T cells and production of proinflammatory cytokines and/or autoantibodies. Consequently, B lineage cells have been identified as therapeutic targets in autoimmune diseases. B cell depleting strategies have proven beneficial in the treatment of rheumatoid arthritis (RA), systemic lupus erythematous (SLE), ANCA-associated vasculitis (AAV), multiple sclerosis (MS), and a wide range of other immune-mediated inflammatory diseases (IMIDs). However, not all patients respond to treatment or may not reach (drug-free) remission. Moreover, B cell depleting therapies do not always target all B cell subsets, such as short-lived and long-lived plasma cells. These cells play an active role in autoimmunity and in certain diseases their depletion would be beneficial to achieve disease remission. In the current review article, we provide an overview of novel strategies to target B lineage cells in autoimmune diseases, with the focus on rheumatic diseases. Both advanced therapies that have recently become available and more experimental treatments that may reach the clinic in the near future are discussed.

Keywords: B cells; autoantibodies; autoimmune diseases; plasma cells; rheumatic diseases.

Figure 1

Selection of novel B‐cell targeting therapeutic strategies in autoimmune diseases. Pink, receptors on the B cell membrane; green, biologic‐based therapies (bispecific antibody in darker green); orange, ligands; gray, CAR T cell; white, intracellular signaling molecules; coral, small molecule inhibitors. Abbreviations: BAFF, B cell activating factor; BAFF‐R, B cell activating factor receptor; TACI, transmembrane activator and cyclophilin ligand interactor; BCR, B cell receptor; BTK, Bruton's tyrosine kinase; CAR, chimeric antigen receptor.