title: Rheumatoid factor in idiotypic regulation of autoimmunity.
abstract: OBJECTIVE
  Rheumatoid factor (RF) is known to be heterogeneous, and RFs detected by various methods exhibit different characteristics. In addition to interacting with the Fc region of immunoglobulin G (IgG), certain RFs are able to recognize idiotypes of antibodies. Given the important role of idiotypic interactions in regulating autoimmunity, we hypothesize that RF is involved in regulation of lymphocyte activity against autoimmune disease-inducing antigens via idiotype-anti-idiotype interactions with these lymphocytes.
  
  
  METHODS
  RF level and the existence of idiotype-anti-idiotype interactions between RF and antibodies to autoimmunity-inducing antigens were studied in rats resistant and sensitive to collagen-induced arthritis, encephalomyelitis and atherosclerosis. RF was assayed by agglutination of tanned IgG-loaded erythrocytes.
  
  
  RESULTS
  Rat resistance to autoimmune disease is associated with high RF production during the initiation of the immune response, and a low RF level during this period may be a preclinical marker of experimental autoimmune disease manifestation. RF-containing sera compete with an antigen if the RF-containing sera were obtained from rats immunized with that antigen, and they non-specifically inhibit binding of different antigen-antibody pairs. This suggests that RFs are anti-idiotypic antibodies that carry two kinds of paratopes: a particular paratope that recognizes the antigen-binding sites of antibodies, and a shared paratope that serves to recognize the recurrent idiotype on antibodies. Antigenic epitopes for the shared RF paratope can be created in the hinge region of Fc fragments of homologous IgG.
  
  
  CONCLUSIONS
  RF detected by agglutination of tanned IgG-loaded erythrocytes is involved in negative idiotypic regulation of lymphocytes specific to autoimmunity-inducing antigens.
authors.affiliation: Department of Immunology and Cell Biology, Udmurt State University, Izhevsk, Russia.
authors.forename: Liubov
authors.initials: L
authors.lastname: Beduleva
authors.affiliation: Department of Immunology and Cell Biology, Udmurt State University, Izhevsk, Russia.
authors.forename: Igor
authors.initials: I
authors.lastname: Menshikov
authors.affiliation: Department of Immunology and Cell Biology, Udmurt State University, Izhevsk, Russia.
authors.forename: Elena
authors.initials: E
authors.lastname: Stolyarova
authors.affiliation: Department of Immunology and Cell Biology, Udmurt State University, Izhevsk, Russia.
authors.forename: Kseniya
authors.initials: K
authors.lastname: Fomina
authors.affiliation: Department of Immunology and Cell Biology, Udmurt State University, Izhevsk, Russia.
authors.forename: Olga
authors.initials: O
authors.lastname: Lobanova
authors.affiliation: Department of Immunology and Cell Biology, Udmurt State University, Izhevsk, Russia.
authors.forename: Pavel
authors.initials: P
authors.lastname: Ivanov
authors.affiliation: Department of Immunology and Cell Biology, Udmurt State University, Izhevsk, Russia.
authors.forename: Alexey
authors.initials: A
authors.lastname: Terentiev
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001169:Arthritis, Experimental / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology* / Q000502:physiology; D016572:Cyclosporine / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D007114:Immunization; D007074:Immunoglobulin G / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012217:Rheumatoid Factor / Q000187:drug effects / Q000276:immunology*; D012680:Sensitivity and Specificity
chemical_list: D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D007074:Immunoglobulin G; D016572:Cyclosporine; D012217:Rheumatoid Factor
keywords: IgG-coated tanned erythrocytes; autoimmunity; idiotypic regulation; rheumatoid factor