title: B-cells and their targeting in rheumatoid arthritis--current concepts and future perspectives.
abstract: Rheumatoid arthritis (RA) is a chronic, autoimmune disease that affects primarily the joints and without proper treatment results in their progressive destruction. In addition to T-cells, B-cells play a central role in the pathogenesis of this disease. The synovial tissue is an active site of B-cell accumulation, plasma cell differentiation and in situ antibody-production in RA. As part of the complex role of B-cells in the joints and synovial membrane of RA patients, B cells secrete chemokines and cytokines and may function as antigen presenting cells. The multifaceted pathogenic function of B-cells identifies them as excellent targets for immunosuppressive therapy. B-cell targeting involves a wide spectrum of molecules, for example the B-cell antigen CD20 that allows specific and effective B-cell depletion. Another target, CD79, expressed by B-cell and plasma cell precursors is an obvious candidate that induces apoptosis as well as inhibition of B-cell receptor (BCR) activation and possibly depletion of ectopic germinal centers (GC). Inhibition of B-cell co-stimulatory molecules such as CD40, CD80/86 and ICOS, can lead to diminished B-cell activation. Moreover, anti-chemokine and anti-cytokine therapies can be efficacious in RA by the disruption of B-cell activation and autoantibody production, B-cell synovial migration and ectopic GC formation. Finally, targeting the signal transduction pathways required for proximal BCR signaling has also been found efficacious in early clinical trials in RA. Even so, some B cells inhibit immune responses, these regulatory B cells may play a part in immune regulation in patients and it is unclear what effects B cell depletion strategies have in terms of such B cell subsets. This review discusses current strategies of targeting B-cells as therapeutic candidates in the management of RA. Better insights into the pathogenic role of B-cells provide efficacious opportunities to improve both therapy and prognosis of patients with RA.
authors.affiliation: Institute of Immunology, Rikshospitalet, Oslo University Hospital, Sognsvannsveien 20, Oslo, Norway.
authors.forename: Britt
authors.initials: B
authors.lastname: Nakken
authors.forename: Ludvig A
authors.initials: LA
authors.lastname: Munthe
authors.forename: Yrjö T
authors.initials: YT
authors.lastname: Konttinen
authors.forename: Anna Klokk
authors.initials: AK
authors.lastname: Sandberg
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Szekanecz
authors.forename: Philip
authors.initials: P
authors.lastname: Alex
authors.forename: Peter
authors.initials: P
authors.lastname: Szodoray
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D018951:Antigens, CD20 / Q000276:immunology / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D001323:Autoantibodies / Q000096:biosynthesis / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D051925:CD79 Antigens / Q000276:immunology / Q000378:metabolism; D002986:Clinical Trials as Topic; D006801:Humans; D007167:Immunotherapy; D008213:Lymphocyte Activation; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D018951:Antigens, CD20; D001323:Autoantibodies; D051925:CD79 Antigens