Targeting B Cells and Plasma Cells in Autoimmune Diseases

Abstract

Success with B cell depletion using rituximab has proven the concept that B lineage cells represent a valid target for the treatment of autoimmune diseases, and has promoted the development of other B cell targeting agents. Present data confirm that B cell depletion is beneficial in various autoimmune disorders and also show that it can worsen the disease course in some patients. These findings suggest that B lineage cells not only produce pathogenic autoantibodies, but also significantly contribute to the regulation of inflammation. In this review, we will discuss the multiple pro- and anti-inflammatory roles of B lineage cells play in autoimmune diseases, in the context of recent findings using B lineage targeting therapies.

The short‐term efficacy of combined treatments targeting B cell and plasma cell in severe and refractory Anti‐N‐methyl‐D‐aspartate receptor encephalitis: Two case reports

“…Researches have shown that for antibody‐related autoimmune diseases, the combined treatment strategy targeting B cells and plasma cells is superior to B‐cell depletion therapy alone . Based on our clinical observations, we propose that it also can improve the prognosis of severe and refractory anti‐NMDAR encephalitis.…”

“…Since anti‐NMDAR encephalitis is mainly mediated by humoral immunity, treatments targeting B cells and plasma cells are therapeutic . Rituximab is a monoclonal antibody directed against the CD20 surface antigen expressed on pre‐B cells, mature B cells, and memory B cells, but not plasma cells . Preliminary data suggested that the protracted clinical course of anti‐NMDAR encephalitis is due to antibody production by long‐lived plasma cells.…”

“…2 Rituximab is a monoclonal antibody directed against the CD20 surface antigen expressed on pre-B cells, mature B cells, and memory B cells, but not plasma cells. 5 Preliminary data 6 suggested that the protracted clinical course of anti-NMDAR encephalitis is due to antibody production by long-lived plasma cells. However, long-lived plasma cells are not affected by conventional immunosuppressive drugs such as steroids or cyclophosphamide, or by B-cell depletion.…”

Identifying novel B-cell targets for chronic inflammatory autoimmune disease by screening of chemical probes in a patient-derived cell assay

“…Targeting B cells and their differentiation into antibody-producing plasmablasts could constitute a promising treatment strategy for autoimmune diseases [8]. In this study, we intestigate the potential of novel chemical probes targeting epigenetic regualtors and thereby identify novel druggable tagets with the potential to modulate B-cell functionality also in B cells from autoimmune patients that may otherwise be more resistant to modulation.…”

“…Consequently, several B-cell targeting therapies have been evaluated and some have moved forward to clinical development [8]. B-cell depletion by the anti-CD20 targeting monoclonal rituximab is approved for treatment of patients with rheumatoid arthritis and anti-neutrophil cytoplasmic antibody (ANCA)-vasculitis and is commonly used off-lable in several autoimmune conditions, but failed to meet the efficacy end-point in SLE.…”