The effect of targeted rheumatoid arthritis therapies on anti‐citrullinated protein autoantibody levels and B cell responses. (6th June 2013)

• Record Type: Journal Article
• Authors: Modi, S.; Soejima, M.; Levesque, M. C.
• Is Part Of: Clinical and experimental immunology. Volume 173:Number 1(2013:Jul.)
• Page Start: 8
• Page End: 17
• Publication Date: 2013-06-06
• Subjects: anti‐citrullinated protein autoantibodies -- biologic therapy -- rheumatoid arthritis -- rheumatoid factor; Immunopathology -- Periodicals; 616.079
• DOI: 10.1111/cei.12114
• Languages: English
• ISSNs: 0009-9104

Abstract

Summary: Rheumatoid arthritis (RA) is a complex inflammatory disorder associated with synovitis and joint destruction that affects an estimated 1·3 million Americans and causes significant morbidity, a reduced life‐span and lost work productivity. The use of biological therapies for the treatment of RA is costly, and the selection of therapies is still largely empirical and not guided by the underlying biological features of the disease in individual patients. The synovitis associated with RA is characterized by an influx of B and T cells, macrophages and neutrophils and the expansion of fibroblast‐like synoviocytes, which form pannus and lead to cartilage and bone destruction. RA is associated with synovial production of rheumatoid factor (RF) and anti‐citrullinated protein autoantibodies (ACPA) and with the production of inflammatory cytokines, including interleukin (IL)‐1, IL‐6, IL‐17 and tumour necrosis factor (TNF)‐α, which are targets for RA therapeutics. Recent ideas about the pathogenesis of RA emphasize a genetic predisposition to develop RA, a preclinical phase of disease that is associated with the production of ACPA and the development of symptomatic disease following inflammatory initiating events that are associated with expression of citrullinated epitopes in the joints of patients. However, we still have a limited understanding of the cytokine and intracellular pathways that regulate ACPA levels. In humans, therapy with biological agents affords a unique opportunity to better understand the cytokine and signalling pathways regulating ACPA levels and the impact of ACPA level changes on disease activity. In this study we summarize the effect of RA therapies on ACPA levels and B cell responses.