title: Rheumatoid factor revisited.
abstract: OBJECTIVE
  Initial studies of the pathogenesis of rheumatoid arthritis focused on the role of rheumatoid factor and immune complex-associated vasculitis and synovitis. Subsequent work has delineated T cell responses, the role of cytokines, chemokines, and the aggressive nature of rheumatoid synovitis. Recent findings underscore the importance of humoral immunity in this entity and are the subject of this review.
  
  
  RESULTS
  By the discovery of anti-cyclic citrullinated peptide, anti-RA33, and anti-GPI antibodies in the human and mouse systems, respectively, the impact of humoral autoimmunity in rheumatoid arthritis regained remarkable interest. This review summarizes recent insights into humoral autoimmunity in rheumatoid arthritis in the context of the generation of rheumatoid factors, including B cell activation via toll-like receptors and genetic predispositions that can trigger the induction of rheumatoid arthritis. The generation of rheumatoid factors that can also be found during host defense against infectious agents and under pathologic conditions, such as rheumatoid arthritis, Sjögren syndrome, and hepatitis C-associated mixed cryoglobulinemia after hepatitis C infection is likely the result of genetic predispositions and the intensity of the (primary) immune reaction. Models of the role of rheumatoid factors in health and disease, including related lymphomagenesis, will be discussed.
  
  
  CONCLUSIONS
  In patients with rheumatoid arthritis, the induction of rheumatoid factors can be taken as an indicator of severe disease with a striking involvement of B cell activation. Very recent clinical trials using B cell depletion support the concept that humoral immunity, as evidenced by the production of rheumatoid factors, plays a significant role in the course of the disease.
authors.affiliation: Department of Medicine/Division of Rheumatology, Ludwigs-Maximilian University Munich, Pettenkoferstrasse 8a, D-80336 Munich, Germany. thomas.doerner@med.uni-muenchen.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Dörner
authors.forename: Karl
authors.initials: K
authors.lastname: Egerer
authors.forename: Eugen
authors.initials: E
authors.lastname: Feist
authors.forename: Gerd R
authors.initials: GR
authors.lastname: Burmester
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D012217:Rheumatoid Factor / Q000276:immunology*
chemical_list: D012217:Rheumatoid Factor