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Immune complex induced IgG1-rheumatoid factor production
Stockholm University.
2000 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Rheumatoid arthritis is a chronic crippling disease mainly characterised by inflammation in the joints. Most patients with rheumatoid arthritis are seropositive, i.e. have increased serum levels of antibodies against the constant part of IgG, so called rheumatoid factors (RF). The presence of RF in patients with rheumatoid arthritis has been correlated with increased destruction of the joint, as well as increase in vasculitis. Many animal models for arthritis exist, but very few exhibit elevated levels of RF. We have developed a mouse model where injection of rheumatoid factor-containing immune complexes from the synovial fluid of patients with rheumatoid arthritis (RA-SF) induced a massive and selective IgG1-RF production in mice from certain strains, prone to develop autoimmune diseases. In addition, when large artificial RF-like (antibody-antibody) immune complexes were used, all tested mice produced IgG1-RF. In this study, this model was used to determine the involvement of different cells and molecules in the rheumatoid factor production as well as the mechanism for the selective IgG1 antibody response induced. We found that induction of IgG1-RF synthesis by large artificial RF-like immune complexes was a T-cell dependent response, as the IgG1-RF production was completely abrogated in CD4+ T cell depleted mice. In addition it was found that the response in FcgRI and III deficient mice was lower compared to wild type mice, whereas the IgG1-RF levels in complement depleted mice were not affected. These findings imply that the IgG1-RF response was partly dependent on the presence of FcgR I and III, but independent of the activity of complement. Interleukin 4, a known switch factor for IgG1 in mice, was also without significance, as evident from IL-4 deficient mice, showing that other cytokines are involved in the IgG1 antibody switch.

Furthermore, the continuous production of IgG1-RF observed in autoimmune prone mice was found to be associated with delayed clearance of the injected immune complexes. This may be of relevance in patients with rheumatoid arthritis, since immune complexes commonly found in the joints of these patients further can stimulate rheumatoid factor production. Moreover, it was found that the ability of mice to respond to RA-SF was linked to the polymorphism in the promoter region of the FcgRIIB gene. Since FcgRIIb functions as a negative regulator of antibody synthesis, the corresponding Fc receptor in humans might be involved in the regulation of rheumatoid factor production in patients with rheumatoid arthritis.

Place, publisher, year, edition, pages
Stockholm: Stockholm University, 2000. , 69 p.
National Category
Research subject
URN: urn:nbn:se:su:diva-70281ISBN: 91-7265-169-5OAI: diva2:480256
Public defence
2000-10-20, 10:00
Härtill 4 uppsatserAvailable from: 2012-01-19 Created: 2012-01-19 Last updated: 2012-01-19Bibliographically approved

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