title: Induction of immune tolerance by oral IVIG.
abstract: In the last years evidence has been provided for the importance of B cells in the pathogenesis of rheumatoid arthritis (RA). Several studies have supported the concept that humoral immunity, manifested by the production of autoantibodies, such as rheumatoid factors (RFs), plays a significant role in the course of the disease. Specific targeting of autoantibody-producing B cells, such as RF-producing B cells, should therefore be a promising new approach in the treatment of RA. We used a mouse model to induce human RF responses and asked the question whether oral treatment with the antigen (human IgG) recognized by RFs could induce immune tolerance to RF responses. Balb/c mice were orally treated with polyvalent human IgG before and after immunization with insoluble immune complexes (ICs) that triggered the induction of RFs. Serum titers of RFs were significantly reduced after both primary and booster immunization when human IgG was given as a single oral dose or continuously in drinking water. Continuous treatment with human IgG even prevented booster effects on RFs when treatment started after primary immunization. Treatment with IgG fragments provided evidence that the observed effect of human IgG was mediated by the Fc part and not the Fab part of IgG. Furthermore, transfer of spleen cells obtained from mice after oral treatment with human IgG suppressed RF responses in recipient mice. These data give promising indications that oral human IgG might represent an alternative approach for immunosuppressive B-cell targeted therapies in RA.
authors.affiliation: Baxter AG, Vienna, Austria.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Maier
authors.forename: Birgit M
authors.initials: BM
authors.lastname: Reipert
authors.forename: Tina
authors.initials: T
authors.lastname: Novy-Weiland
authors.forename: Willfried
authors.initials: W
authors.lastname: Auer
authors.forename: Bernhard
authors.initials: B
authors.lastname: Baumgartner
authors.forename: Eva M
authors.initials: EM
authors.lastname: Muchitsch
authors.forename: Christian
authors.initials: C
authors.lastname: Fiedler
authors.forename: Leopold
authors.initials: L
authors.lastname: Grillberger
authors.forename: Hans Peter
authors.initials: HP
authors.lastname: Schwarz
mesh_terms: D000284:Administration, Oral; D019264:Adoptive Transfer; D000818:Animals; D005169:Factor VIII / Q000276:immunology; D005260:Female; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects*; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology; D007141:Immunoglobulin Fc Fragments / Q000494:pharmacology; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D012217:Rheumatoid Factor / Q000097:blood
chemical_list: D007140:Immunoglobulin Fab Fragments; D007141:Immunoglobulin Fc Fragments; D016756:Immunoglobulins, Intravenous; D005169:Factor VIII; D012217:Rheumatoid Factor