B Cells as a Therapeutic Target in Paediatric Rheumatic Disease.

Meredyth G Ll Wilkinson,Elizabeth C Rosser

doi:10.3389/fimmu.2019.00214

Abstract

B cells carry out a central role in the pathogenesis of autoimmune disease. In addition to the production of autoantibodies, B cells can contribute to disease development by presenting autoantigens to autoreactive T cells and by secreting pro-inflammatory cytokines and chemokines which leads to the amplification of the inflammatory response. Targeting both the antibody-dependent and antibody-independent function of B cells in adult rheumatic disease has led to the advent of B cell targeted therapies in clinical practice. To date, whether B cell depletion could also be utilized for the treatment of pediatric disease is relatively under explored. In this review, we will discuss the role of B cells in the pathogenesis of the pediatric rheumatic diseases Juvenile Idiopathic Arthritis (JIA), Juvenile Systemic Lupus Erythematosus (JSLE) and Juvenile Dermatomyositis (JDM). We will also explore the rationale behind the use of B cell-targeted therapies in pediatric rheumatic disease by highlighting new case studies that points to their efficacy in JIA, JSLE, and JDM.

Highlights

B CELLSThe most well-defined function of B cells is their ability to produce antibodies as part of the humoral immune response
All trials investigating its efficacy of Abatacept in adult-onset SLE have not reached their primary end-point, this is likely to be to problems in clinical trial design in lupus, to those conducted with Rituximab, as there is some evidence it suppresses the severity of nephritis [101]
Abatacept treatment is likely to affect multiple immune cell subsets, these data demonstrate a decisive effect of this drug on the B cell compartment

Summary

B Cells as a Therapeutic Target in Paediatric Rheumatic Disease

Reviewed by: Zoltan Jakus, Semmelweis University, Hungary Marko Radic, University of Tennessee College of Medicine, United States. In addition to the production of autoantibodies, B cells can contribute to disease development by presenting autoantigens to autoreactive T cells and by secreting pro-inflammatory cytokines and chemokines which leads to the amplification of the inflammatory response. Targeting both the antibody-dependent and antibody-independent function of B cells in adult rheumatic disease has led to the advent of B cell targeted therapies in clinical practice. In some B cells, activation induces class-switching, the process by which B cells change their immunoglobulin class from one to another (i.e., IgM to IgG/IgA/IgE) All together, these diverse functions within the adaptive immune response make B cells an important target for investigation in rheumatic disease

B Cells in Paediatric Rheumatic Disease

B Cell Depletion Therapy

Summary approved

Findings

CONCLUDING REMARKS